U of WM Tom Yin Grant Documents Part 3

Notice of Award
RESEARCH Issue Date: 03/16/2009

Department of Health and Human Services
National Institutes of Health
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
Grant Number: 5R01DC003693-06 REVISED
Prlnclpallnvestlgator(s):
LUIS C POPULlN, PHD
Project Title: Multisensory Processing in the Behaving Preparation
Award e-malled to: NIH@rsp.wisc.edu
Budget Period: 12/01/2008 - 11/30/2009

Project Period: 09/01/1999 - 11/30/2010
Dear Business Official:
The National Institutes of Health hereby revises this award to reflect an increase in the amount of
$31,237 (see "Award Calculation" in Section I and "Terms and Conditions" In Secllon III) to
UNIVERSITY OF WISCONSIN MADISON in support of the above referenced project. This award
is pursuant to the authority of 42 USC 241 42 CFR 52 and is subject to the requirements of this
statute and regulation and of other referenced, incorporated or attached terms and conditions.
Acceptance of this award including the "Terms and Condillons" is acknowledged by the grantee
when funds are drawn down or otherwise obtained from the grant payment system.
Each publication, press release or other document that cites results from NIH grant-supported
research must Include an acknowledgment of NIH grant support and disclaimer such as "The
project'described was supported by Award Number R01DC003693 from the Nallonallnstitute On
Deafness And Other Communication Disorders. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the National Institute On Deafness
And Other Communication Disorders or the Nationallnstltutes of Health."
Award recipients are required to comply with the NIH Public Access Policy. This inciudes
submission to PubMed Central (PMC), upon acceptance for publication, an electronic version of a
final peer-reviewed, manuscript resulting from research supported in whole or in part, with direct
costs from National Institutes of Health. The author's final peer-reviewed manuscript is defined as
'the final version accepted for journal publication, and includes all modifications from the publishing
peer review process. For additional information, please visit http://publicaccess.nih.gov/.
Award recipients musfpromote objectivity in research by establishing standards to ensure that the
design, conduct and reporting of research funded under NIH-funded awards are not biased by a
conflicting financial interest of an Investigator. Investigator is defined as the Principal Investigator
and any other person who is responsible for the design, conduct, or reporting of NIH-funded
research or proposed research, including the Investigator's spouse and dependent children.
Awardees must have a written administrative process to identify and manage financial conmct of
interest and must inform Investigators of the conflict of interest policy and of the Investigators'
responsibilities. Prior to expenditure of these awarded funds, the Awardee must report to the NIH
Awarding Component the existence of a conflicting interest and within 60 days of any new
conflicting interests identified after the initial report. Awardees must comply with these and all other
aspects of 42 CFR Part 50, Subpart F. These requirements also apply to subgrantees, contractors,
or collaborators engaged by the Awardee under this award. The NIH website
http://grants.nih.gov/grantsfpolicvlcoifindex,htm provides additional information.
, Page-I
+-~*~1~~4
2011-04-22 000167
If you have any questions about this award, please contact the individual(s) referenced in Section
IV.
Sincerely yours,
Sherry Dabney
Grants Management Officer
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
Additional information follows
Page-2
2011-04-22 000168
SECTION 1- AWARD DATA - 5R01DC003693·06 REVISED
Award Calculation (U.S. Dollars)
Federal Direct Costs $212,500

Federal F&A Costs $99,875
Approved Budget $312,375
Federal Share $312,375
TOTAL FEDERAL AWARD AMOUNT .. $312,375
AMOUNT OF THIS ACTION (FEDERAL SHARE) $31,237
SUMMARY TOTALS FOR ALL YEARS

YR THIS AWARD CUMULATIVE TOTALS
6 $312,375 $312,375
7 $312,375 $312,375
..
Recommended future year total cosl support, subject to the availability of funds and satisfactory
progress of the project
Fiscal Information:
gEDANu:er:
fEIN: :~73
ocumen umber: ROCUO 3B
Fiscal Year: 2009
IC CAN 2009 2010

C 472510 312,375 312,375
Recommended future year total cost support, subject to the availability of funds and satisfactory
progress of the project
NIH Administrative Data:

PCC: HR61 1 OC: 414E 1 Processed: SDENNISON 03/13/2009
SECTION 11- PAYMENT/HOTLINE INFORMATION - 5R01DC003693·06 REVISED
For payment and HHS Office of Inspector General Hotline information, see the NIH Home Page at
htip:lIgranls.nih.gov/grants/poHcy/awardconditions.htm
SECTION /11- TERMS AND CONDITIONS - 5R01DC003693·06 REVISED
This award is based on the application submitted to, and as approved by, NiH on the above·tltled
project and is subject 10 the terms and conditions incorporated either directly or by reference in the
following:
a. The grant program legislation and program regulation cited in this Notice of Award.
b. Conditions on activities and expenditure of funds in other statutory requirements, such as
those included in appropriations acts.
c. 45 CFR Part 74 or 45 CFR Part 92 as applicable.
d. The NIH Grants Policy Statement, including addenda in effect as of the beginning date of
the budget period.
e. This award notice, INCLUDING THE TERMS AND CONDITIONS CITED BELOW.
(See NIH Home Page at 'http://grants.nih.gov/grants/policy/awardconditions.htm' for certain

references cited above.)
This institution is a signatory to the Federal Demonstration Partnership (FOP) Phase V Agreement
which requires active institutional participation in new or ongoing FOP demonstrations and pilots.
An unobligated balance may be calTled over into the next budget period without Grants
Management Officer prior approval.
This grant is subject to Streamlined Noncompeting Award Procedures (SNAP).
Page·3
2011-04-22 000169
In accordance with P.L. 110-161, compliance with the NIH Public Access Policy is now mandatory.
For more Information, see NOT-OD-08-033 and the Public Access website:
http://publicaccess,nilhgov/.
Treatment of Program Income:

Additional Costs
SECTION IV - DC Special Terms and Conditions - 5R01 DC003693·06 REVISED
This revised award Increases the total costs authorized consistent with the NIH and NIDCD fiscal
policies for FY2009.
STAFF CONTACTS
The Grants Management Specialist is responsible for the negotiation, award and administration of
this project and for interpretation of Grants Administration pOlicies and provisions. The Program
Official is responsible for the scientific, programmatic and technical aspects of this project. These
individuals work together in overall project administration. Prior approval requests (signed by an
Authorized Organizational Representative) should be submitled in writing to the Grants
Management Specialist. Requests may be made via e-mail.
Grants Management Specialist: Hoai Doan

Email: hoaid@nidcd.nih.govPhone: (301) 435-1404 Fax: (301) 402-1758
Program Official: Christopher Platt

Email: plattc@nldcd.nih.govPhone: (301)496-1804 Fax: (301)402-6251
SPREADSHEET SUMMARY
GRANT NUMBER: 5R01DC003693·06 REVISED
INSTITUTION: UNIVERSITY OF WISCONSIN MADISON
Facilities and Administrative Year 6 Year 7

Costs
&A Cost Rate 1 147% 7%
F&A Cost Base 1 $212,500 212,500
&A Costs 1 $99,875 99,875
Page-4
2011-04-22 000170
THE UNIVERSITY
WISCO---N-SI-N
M A·D ISO N 03/25/2009
To Whom It May Concern:
. the following grant application submitted to NIH

is named on an animal care and use protocol approved on 02111/2009 (3-year approval).
Most Recent Committee Re-review: 02111/2009.
Name of Principal Investigator: Populln, Luis C.
Address: Medical Sciences Ctr., 1300 University Ave., 8385
Title of Grant Application: Multisensory processing In the behaving

preparation
Grant #: pending
Name of Animal Care and Use Committee: SMPH
Name of Chairperson: Dr. Amy Moser
The University of Wisconsin-Madison has an animal welfare assurance on file with the Office for
Protection from Research Risks. The assurance number is A3368-01.
Significant modifications required prior to committee approval of a protocol which was already
submitted to the funding agency are as follows: NONE
Chairperson's Signature: _ _ - =~:. .JL.:.: .: :. J-. LI#e.~ .c: .: . .!~ . : : : ;,:4, $:!f~'j: .I=~
FOAM IIM01498·0·11-08
Research Animal Resources Center

396 Enzyme Institute University of Wisconsin-Madison 1710 University Avenue Madison, Wisconsin 53726-4087
6081262-1238 Fax: 608/265-2698 Email: help@rarc.wisc.€du http://www.rarc.wisc.edu
9
2011-04-22 000171
PI: POPULIN, LUIS C Title: Multisensory Processing in the Behaving Preparation
Received: 03/05/2007 FOA: PA07-070 Council: 10/2007
Competition 10: FOA Title: RESEARCH PROJECT GRANT (PARENT R01)
2 R01 DCOO3693-0SA1 Dual: NS Accession Number: 2978361
IPF: 578503 Organization: UNIVERSITY OF WISCONSIN MADISON
Former Number: Department: ANATOMY-GEN
IRG/SRG: SMI AIDS:N Expedited: N
Subtotal Direct Costs Animals: Y New Investigator: N

(excludes consortium F&A) Humans: N Early Stage Investigator: N
Year 5: 250,000 Clinical Trial: N
Year 6: 250,000 Current HS Code: 10
Year 7: 250,000 HESC: N
Year 8: 250,000
Year 9: 250,000
SeniorlKey Personnel: Organization: Role Category:
LUIS POPULIN The Board of Regents of the University PO/PI

of Wisconsin System
2011-04-22 000172
APPLICATION FOR FEDERAL ASSISTANCE 2. DATE SUBMITTED Applicant Ident~fier
SF 424 (R&R) 02/14/2007

3. DATE RECEIVED BY STATE
35821
State Application Identifier
1.' TYPE OF SUBMISSION
o Pre-application • Application 4. Federal Identifier
o Changed/Corrected Application DC003693
5. APPLICANT INFORMATION .. Organizational DUNS:161202122

.. Legal Name: The Board of Regents of the University of Wisconsin System
Department: Division:
.. Street1: 21 N. Park Street Street2: Suite 6401
.. City: Madison County: Dane * State: WI: Wisconsin
Province: • Counlry: USA: UNITED STATES • ZIP I Postal Code:
53715-1218
Person to be contacted on matters involving this application

Prefix: .. First Name: Middle Name: .. Last Name: Suffix:
Ms. JENNIFER RODIS
• Phone Number: 608·262-4990 Fax Number: 608-262-5111 Email: rodis@rsp.wisc,edu
6.' EMPLOYER IDENTIFICATION NUMBER (EIN) or (TIN): 7 •• TYPE OF APPLICANT
H: PublicJState Controlled Institution of Higher EdUcation
8.' TYPE OF APPLICATION: o New Other (Specify):
• Resubmission o Renewal o Continuation QRevision
o Women Owned
Small Business Organization Type
o
Socially and Economically Disadvantaged
If Revision, mark appropriate box(es). 9 .• NAME OF FEDERAL AGENCY:
o A. Increase Award o B. Decrease Award o C. Increase Duration National Institutes of Health
o D. Decrease DurationQ E. Other (specify): 10. CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER:
TITLE: Research Project. Grant (Parent R01)
"" Is this application being submitted to other agencies? U Yes • No
What other Agencies? . .
11.' DESCRIPTIVE TITLE OF APPLICANT'S PROJECT:
Multisensory Processing In the Behaving Preparation
12.• AREAS' AFFECTED BY PROJECT (cities, counties, states, etc.)
NfA
13. PROPOSED PROJECT: 14. CONGRESSIONAL DISTRICTS OF:
"" Start Date "" Ending Date a. "" Applicant b. "" Project
09/01/2007 08/31/2012 02 002
15. PROJECT DIRECTOR/PRINCIPAL INVESTIGATOR CONTACT INFORMATION
Prefix: "" First Name: Middle Name: "" Last Name: Sullix:
Dr. LUIS C POPULIN
Posilionmlle: ASSISTANT PROFESSOR "" Organization Name: The Board of Regents of the University of Wisconsin System
Departmenl: ANATOMY-GEN Division:
• S~eet1: 1300 UNIVERSITY AVE S~eel2: 8385 MEDICAL SCIENCES CTR
• City: MADISON County: * State: WI: Wisconsin
Province: • Country: USA: UNITED STATES • ZIP I Postal Code:
53706-1509
• Phone Number: (608) 265-6451 Fax Number: (608) 262-7306 • Email: LPOPULlN@WISC.EDU
Reeefved Dale: Time Zone: GMT·S OMe Number: 4040.0001

Tracking Number: Funding Opportunity Number:
Expiration Dale: 04l30{2008
2011-04-22 000173
SF 424 (R&R) APPLICATION FOR FEDERAL ASSISTANCE
Page 2
16. ESTIMATED PROJECT FUNDING 17. 'IS APPLICATION SUBJECT TO REVIEW BY STATE EXECUTIVE ORDER 12372 PRO·
CESS?
a. YES
a. ,. Total Estimated Project Funding $1,837,500.00 0 THIS PREAPPLICATION/APPLICATION WAS MADE AVAILABLE TO THE
STATE EXECUTIVE ORDER 12372 PROCESS FOR REVIEW ON:
b. ~ Total Federal & Non·Federal Funds $1,837,500.00 DATE:
C. * Estimaled Program Income $0.00 b. NO
•
PROGRAM IS NOT COVERED BY E.O. 12372; OR
0 PROGRAM HAS NOT BEEN SELECTED BY STATE FOR REVIEW
18. By signing this application, I certify (1) to the statements contained In the list of certifications" and (2) that the statements herein are true. complete
and accurate to the best of my knowledge. I also provide the required assurances * and agree to comply with any resulting terms if I accept an
award. I am aware that any false, fictitious, or fraudulent statements or claims may subject me to criminal, civil, or administrative penalties. (U.S.
Code, Title 18, Section 1001)
• * I agree
• The list 01 certifications and asSUflIn<:6S, or an Internet sits where you may obtain tN$li$~ Is contained In the announcement or agency specific insltvc/ions.
19. Authorized Representative

Prejh(: • First Name: Middle Nam.·
,
Suffix:
· rOSI
'4J..
lontI IlES:
. "'" "" • . ,N . The Board of Reaents ~f Ih , 1,
1
Departml? ;;search & Snonsored Programs Divisi01![aiO S.~~
• Street1
• City: MADISON
1 Street~
County: ane
] • State: WI: Wisconsin
Province: 'Country: USA: UNITED STATES ' ZIP 1 Postal Code:
537151218
• Phone Number
* 1\ 1 Fax Numbei
* J • Email: cayuse@rsp.wlsc.edu
, Signature AuthO:d R.e[~··rtlve. • Date Signed
03/0512007
20. Pre..appllcatlon File Name: Mime Type:

21. Attach an additional list of Project Congressional Districts if needed.
File Name: Mime Type:
TrackIng Number: Funding Opportunity Number. Received Dale: Time Zone: GMT·S OMS Number: 40040.()001
expiration Dale: 0413012008
2011-04-22 000174
Principal Investigator/Program Director (Last, first, middle): POPULlN, LUIS, C
424 R&R and PHS·39B Specific

Page Numbers
Table Of Contents
SF 424 R&R Face Page··················································................................................................. .
Table of Contents u . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 3
Research & Related ProjecUPerformance Site Location(s)·.········.·.... •·· .. ······•··••· ..••·••••.. •··•· ................ .. 4
Research & Related Other Project Informatlon··································-····· .. •• ....................................... . 5
Project Summary/Abstract (Description)·····-············ ...... ················~··....................... . 6
Public Health Relevance Statement (Narrative attachment) .. ······u.............................. 7
Facilities & Other Resources.····· ..•••·••·•·• ..··············~· ..·· .. ······•................... . 8
Eq uip ment································ .. ·•·•··•· .. ··•..•··• .•.••..••.....

Research & Related Senior/Key Person···························· .. ·······•·····•··••• ............................................ . 10
Biographical Sketches for each listed Senior/Key Person···················_········ .. ·..•· .. •••·••·•· .. • 12
PHS 398 Specific Cover Page Supplement··········· oaoa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
PHS 398 Specific Modular Budget····················· .. ·••·•··•····••········•··· ..................................................... . 16
Personnel Justification········································· •.....•.••.•....•....•.•.• 20
PHS 398 Specific Research Pian·················································· ..............................._ .................... . 21
Introduction to Revised/Supplemental Application·····················.... ··••··••·••·•• .. •··•• .......... . 24
Specific Aims··················································.••....••..••.••• 27
Significance and Related R&D···~····· .. ··•··•·•••••··•··•·••··•·••·•·•.. ···---···••.•••••.••• 28

Experimental/Research Design and Methods·················· ..·················_···· ao
•••••••••••••••••••••• 34
Vertebrate Animals·························· ..·•••••···••••······· ••....•. ~ ........ . 45
Bibliography & References Cited·········· to . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . _ •••• _ ••••••• 47
PHS 398 Checklist·············································· .....•••.••...•..•..• 52
Table of Contents Page 3
2011-04-22 000175
Principallnvestigator/Program Director (Last, first, middle): POPULlN, LUIS, C
RESEARCH & RELATED Project/Performance Site Location(s)
ProjecVPerformance Site Primary Location

Organization Name: The Board of Regents of the University of Wisconsin System
* Street1: 1300 University Ave Street2:
* City: Madison County: Dane * State: WI: Wisconsin
• Counl!y: USA: UNITED
Province: STATES
* Zip I Postal Code:
File Name Mime Type
Additional Location(s)
Performance Sites Page 4

Trm:klng Number: OMB Number: 4040..()001
EXpiration Dale: 0413012008
2011-04-22 000176
RESEARCH & RELATED Other Project Information
1. * Are HUman Subjects Involved? 0 Ves • No

1.a. If YES to Human Subjects
Is the IRS review Pending? o Ves o No
IRB Approval Date:
Exemption Number: _1 _ 2 _ 3 _4 _5 _6
Human Subject Assurance Number
~. * Are Vertebrate Animals Used? • Ves 0 No
2.a. If YES to Vertebrate Animals
Is the IACUC review Pending?
IACUC Approval Date:
o
03·07-2006
Ves
• No
Animal Welfare Assurance Number A336801
~. * Is proprietary/privileged information 0 Ves • No

Included in the application?
.B. * Does this project have an actual or potential Impact on
the environment?
0 Ves
• No
.b. If yes, please expJaln:

.c. If this project has an actual or potential impact on the environment. has an exemption been authorized or an environmental assessment (EA) or
environmental Impact statement (EIS) been performed? 0 Ves o No
.d. If yes, please explain:
~.a. * Does this project involve activities outside the U.S. or o Ves • No
partnership with International Collaborators?
.b. If yes, Identify countries;
.c. Optional Explanation:
* Project Summary/Abstract Abslrac11001742443.pdf Mime Type: application/pdf
* Project Narrative ProJeclNarrativel0017q2534.pdf Mime Type: application/pdf
~. Bibliography & References Cited Bibliography1001742444.pdf Mime Type: application/pdf
Facilities & Other Resources Facililles1001742434.pdf Mime Type: application/pdf
10. Equipment Equipmen11001742440.pdf Mime Type: application/pdf
Tracking Number: Other Information Page 5 OMB Number: 4040.{l001

ExplraUon Date: 04130/2008
2011-04-22 000177
Principallnvesligator/Program Director (Last, first, middle): POPUlIN, LUIS, C
ABSTRACT
The goal of this project is to extend our knowledge of the neural mechanisms that underlie the integration
of information from different sensory modalities and their transformation into motor commands to generate
gaze shifts. Specifically, we will seek to establish the relationship between the magnitude and timing of
sensory responses, associated motor discharges, and resulting gaze shifts.
The proposed experiments, to be carried out in a newly developed head-unrestrained monkey
preparation, are a natural continuation of those carried out in the behaving, head-restrained cat during the
previous funding period. The change from the cat to. the monkey preparation was dictated by the questions
that arose from our previous work, which cannot be adequately addressed in the cat. The experimental
approach will be to record from single units in the intermediate layers of the superior colliculus (SCi) of
monkeys (1) during the presentation of acoustic, visual, and bimodal stimuli, and (2) while they orient to the
sources of those stimuli.
The proposed work comprises four specific aims: AIM 1 will test the. hypothesis that facilitation of
behavioral responses to bimodal stimuli in primates is mediated by integrative mechanisms that obey linear
(or sub-additive), not super-additive processes. AIM 2 will test the alternative hypothesis that enhanced
bimodal responses are observed in single SC units, but under conditions of high behavioral significance to
the subject. AIM 3 will test the hypothesis that the SC operates in two distinct modes: a detection mode,
characterized by large neuronal responses that increase the likelihood of orienting movements directed to the
source of the stimUli, and an attention-driven mode, characterized by smaller, transient neuronal responses
that provide for fine behavioral control, e.g., stopping the response if changing conditions so require. AIM 4
will test the motor error hypothesis (Sparks, 1986) in the head-unrestrained monkey.
Project Description Page 6
2011-04-22 000178
Principallnvestigator/Program Director (last, first, middle): POPULlN, lUIS, C
PROJECT NARRATIVE
This project is concerned with two of the most fundamental questions facing systems neuroscience: how is
inform~tion from different sensory modalities integrated into a unique and single representation of the
surrounding space, and how is such information used to generate and control movement - specifically, gaze
shifts (coordinated movements of the eyes and head). Furthering our understanding of how nature has
implemented neural solutions to these basic questions will result in the design of better computer-brain
interface devices, prostheses, smart robots, automatic system recognition devices, and ultimately help
neurology/otolaryngology in devising electronic and pharmacological solutions for patients affects with
sensory and sensorimotor integration diseases.
Public Health Relevance Statement Page 7
2011-04-22 000179
Principal Investigator/Program Director (last, first, middle): POPUUN, lUIS, C
FACILITIES
Laboratory. The PI's laborato~ -4- . . pf

the University of Wisconsin
Medical School. It comprises -15 0 square reet, and It IS eqUippea wlln three complete experimental setups
for audio-oculomotor behavioral and physiological experiments. .
Offir The offices of PI Pit-doctoral fellows, computer proarammers, technician, and students are
located__ _ . . . . --.- J .
School_ *'
under the supervision of a Dr. iiiVeierinary Medicine.
_
Anira,. The animals are housed in the animal care facility of the University of Wisconsin-Madison Medical
)rhe facility is operated by experienced staff
Other. Access to the Medical Electronics Lab and The Physics Dept Instrument Shop is available for an
hourly fee. The services provided by these facilities are essential to build, maintain, and adapt our
experimental equipment as needed.
Facilities Page 8
2011-04-22 000180
EQUIPMENT
The PI's laboratory is completely equipped to carry out the proposed work. It consists of three
experimental setups. Each setup consists of a double-walled (3.2 X 3 X 2) m sound proof chamber (Acoustic
Systems, Austin, TX), a phase angle magnetic search coil system (CNC Engineering) with three phase
sensitive detectors, and Tucker Davis Technologies System 3 hardware to present acoustic stimuli. Data
acquisition and stimulus presentation systems are controlled with PCs running custom'software. The array of
electrophysiological equipment for each setup includes: amplifier (BAK Electronics), window discriminator
(Tucker Davis Technologies), audio monitor, analog filters (Krohn Hite, Co), real-time spike sorting system
(Alpha Omega, Nazareth IlIit, Israel), two oscilloscopes (Tektronix), and Narishige microdrives for chronic
recordings.
The computers in the PI's lab include 17 PCs, 2 Macintosh, and a Dell PowerEdge 4040 two-processor
Linux server that runs an Oracle database containing all eye movement and physiological data collected in
the lab. All computers are linked by an intranet served by a windows 2003 server that handles mail, data
backup, and printing services. In addition the PI's lab is equipped with a Lexmark laser printer, an Epson
color printer, and a Hewlett-Packard scanner.
Equipment Page 9
2011-04-22 000181
Principal Investigator/Program Director (Last, first, middle): POPUUN, LUIS, C
RESEARCH & RELATED Senior/Key Person Profile (Expanded)
PROFILE - Project Director/Principal Investigator
Prefix * First Name Middle Name. * Last Name Suffix

Dr. LUIS C POPULIN
Positionmtle: ASSISTANT PROFESSOR Department: ANATOMY-GEN
Organization Name: The Board of Regents of the University of Wisconsin Division:

System
• Slreet1: 1300 UNIVERSITY AVE Slreel2: 63B5 MEDICAL SCIENCES CTR
• City: MADISON County: * State: WI: Wisconsin Province:
• Counlry: USA: UNITED STATES • Zip I Poslal Code: 53706-1509
*Phone Number Fax Number • E-Mail

(60B) 265-6451 (60B) 262-7306 LPOPULlN@WISC.EDU
Credential, e.g., agency login:

* Project Role: PO/PI Other Project Role Category:
File Name Mime Type
*Attach Biographical Sketch Luls_Popuiln1001742437.pdf application/pdf
Attach CUrrent & Pending Support
OMS Number: ~~.(IOO1

Tracking Humber: Key Personnel Page 10
expiration Dale: 0.413012008
2011-04-22 000182
RESEARCH & RELATED Senior/Key Person Profile (Expanded)

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1) Please attach Attachment 1

2) Please aUach Attachment 2
Filename
ADDITIONAL SENIOR/KEY
PERSON PROFILE(S)
MlmeType
Filename
Additional Biographical
Sketch(es) (Senior/Key Per~on)
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Filename
Additional Current and
Pending Support(s)
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Tracking Number: Key Personnel Page 11 OMB Number: 40OW-0001

EXpiration Date: 0413012008
2011-04-22 000183
PrincipallnvestigatorJProgram Director (Last, first, middle): POPULlN, LUIS, C
BIOGRAPHICAL SKETCH
NAME POSITION TITLE

Luis C Populin Assistant Professor
EDUCATIONITRAINING DEGREE YEAR FIELD OF STUDY

IPEF, C6rdoba, Argentina BS 1978 Physical Education
Oregon State University MS 1988 Motor Behavior
University of Wisconsin-Madison PhD 1996 Neuroscience and Kinesiology
University of Wisconsin-Madison Post Doc 1996 Anatomy
POSITIONS AND HONORS

1988-1990 Project Assistant, Motor Behavior Laboratory, Dept. of Kinesiology, University of Wisconsin
1990-1996 Research Assistant, Dept. of Neurophysiology, University of Wisconsin with Dr. Tom Yin
1996-199" Research Associate, Dept. of Anatomy, University of Wisconsin with Dr. John Harting
1997-2003 Assistant Scientist, Dept. of Anatomy, University of Wisconsin, Madison
2003- Assistant Professor, Dept. of Anatomy, University of Wisconsin, Madison
1996 Sigma Xi Graduate Research Award

1997 Fifteen Jerzy E. Rose Neuroscience Award
PUBLICATIONS
Populin LC, Rose DJ, Heath KE (1990) The role of attention in one-handed catching. J Motor Behav 22:149-
158.
Stelmach GE, Populin LC, MUlier F (1990) Postural muscle onset and voluntary movement in the elderly.
Neurosci Lett 117:188-193.
Populin LC, and Yin TCT (1995) Topographical organization of the motoneuron pools that innervate the
muscles of the pinna of the cat. J Comp Neurol 363:600-614.
Yin TCT, Populin LC (1997) Sound localization and pinna movements in the behaving cat. In: Acoustical
Signal Processing in the Central Auditory System (Syka J, ed), pp 399-405. New York: Plenum Press.
Populin LC, Yin TCT (1998) Sensitivity of auditory cells in the superior colliculus to eye position in the
behaving cat. In: Psychological and Physiological Advances in Hearing (Palmer AR, Rees A, Summerfield
AQ, Meddis R, eds), pp 441-448. London: Whurr Publishers.
Yin TCT, Populin LC (1998) Behavioral and physiological studies of sound localization in the cat. In: Central
Auditory Processing and Neural Modeling (Brugge J and Poon P, eds). New York: Plenum Press.
Populin LC, Yin TCT (1998) Behavioral studies of sound localization in the cat. J Neurosci 18: 2147-2160.
Populin LC, Yin TCT (1998) Pinna movements of the cat during sound localization. J Neurosci 18: 4233-
4243.
Populin LC, Yin TCT (1999) Kinematics of eye movements of cats to broadband acoustic targets. J
Neurophysiol 82:955-962.
Smith PH, Populin LC (2001) Fundamental differences between the thalamocortical recipient layers of the cat
auditory and visual cortices. J Comp NeuroI436:508-519.
Populin LC, Tollin DJ, Weinstein JM (2002) Human gaze shifts to acoustic and visual targets. Ann N Y Acad
Sci 956:468-473.
Populin LC Yin TCT (2002) Bimodal interactions in the superior colliculus of the behaving cat. J Neurosci
22:2826-2834.
Populin LC, Tollin DJT, Yin TCT (2004) Effect of eye position on saccades and neuronal responses to
acoustic stimuli in the superior colliculus of the behaving cat. J NeurophysioI92:2151-2167.
Tollin DJ, Populin LC, Yin TCT (2004) Neural correlates of the precedence effect in the inferior colliculus of
behaving cats. J NeurophysioI92:3286-3297.
Tollin OJ, Populin LC, Moore JM, Ruhland JL, Yin TCT (2005) Sound localization performance in the cat: The
effect of training the head. J Neurophysiol 93:1223-1234.
Biosketches Page 12
2011-04-22 000184
Principallnvestigator/Program Director (Last, firsl, middle): POPULlN, LUIS, C
Populin LC (2005) Anesthetics change the excitation/inhibition balance that governs sensory processing in
the cat superior colliculus. J Neurosci 25:5903-5914.
Populin LC (2006) Monkey sound localization: head-restrained versus head-unrestrained orienting. J
Neurosci 26:9820-9832.
Biosketches Page 13
2011-04-22 000185
Principallnvestigalor/Program Director (last, first. middle): POPUlIN, lUIS, C
PHS 398 Cover Page Supplement
OMS Number: 0925-0001

Expiration Dale: 9/30/2007
1. Project Director / Principal Investigator (PO/PI)
Prefix: IDr- * First Name:llUIS

I I
Middle Namej C
I
* last Name: IpOPULli'I I
Suffix:
I I
* New Investigator? eNo OYe.
Degrees: IPhD I I I I I
2. Human Subjects
Clinical Trial? eNo OYe.
* Agency·Defined Phase III Clinical Trial? eNo OYe.
3. Applicant Organization Contact
Person to be contacted on matters involving this application

Prefix: 10 I "* First Name:11 ii \ I
Middle Namej
I
* Last Name: 'I '110 } I
Suffix: I I
* Phone Numberr, ' .-~

)
I Fax Number 1 J I
Email:r, .."" J I
* Title: .G 4- J I
* Street1: ~ ~ l I
Street2: 't :J;J I
:~)
• City:
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County:
I
* State: C ... ==' I
Province: I
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* Country: ~ J * Zip I Postal Code:
I>*=--J I
'1\~,oD~/~ ConY \m~,rrn~ ~ ~~ ~V.

Tracking Number: "* Ctinical Trial & HESC Page 1
2011-04-22 000186
PrincipallnvestigalorlProgram Director (Last, first, middle): POPUlIN, LUIS, C
PHS 398 Cover Page Supplement

OMS Number: 0925·0001
Expiration Date: 913012007
4. Human Embryonic Stem Cells

., Does the proposed project involve hUman embryonic stem cells? OYes
If the proposed project involves human embryonic stem cells, list below th~ registration number of the
specific cellline{s) from the following list: http:{{stemcells.nih.govlregistryfindex.asp . Or, if a specific
stem cell line cannot be referenced al this time, please check the box indicating that one from the registry will be used:
Cell Llne(s): Specific stem cell line cannot be referenced at this time. One from the registry will be used.
Clinical Trial & HESC Page 15

Tracking Number;
2011-04-22 000187
Principallnvestigator/Program Director (last, first, middle): POPULJN, LUIS, C
PHS 398 Modular Budget, Periods 1 and 2

OMB Number: 0925-0001
Expiration Date: 9/30/2007
Budget Period: 1
Start Date: ~9/01/2007 I End Date: ~8/31/2008 I
A. Direct Costs Funds Requested ($)
* Direct Cost less Consortium F&A I 250.000.0~
Consortium F&A I
I
* T alai Direct Costs I 250.000.0~
B. Indirect Costs
Indirect Cost Indirect Cost
Indirect Cost Type Rate (%) Base ($) • Funds Requested ($)
1. IMDTC On-campus I~ I 250.000.0~ I 117.500.0~
2.
I I c::J I II I
3.
I I c::J I II I
4. I I c::J I II I
Cognizant Agency (Agency Name, POC Name and Phone Number) fDHHS, Henry Williams, 214-767-3261
I
Indirect Cost Rate Agreement Date ~8/09/2006 I Total Indirect Costs I 117.500.0~
C. Total Direct and Indirect Costs (A + B) Funds Requested ($) I 367.500.0~
Budget Period: 2
Start Date: ~9/01/2008 End Date: 128/31/2009
I I
~ Direct Cost less Consortium F&A I 250.000.0~
Consortium F&A I I
~ Total Direct Costs
I 250.000.0~
B. Indirect Costs
1. IMDTC On-campus II 47.001 I 250.000.0~ I 117.500.0~
2.
I I c::J I II I
3.
I I c::J I II I
4. I I c::J I II I
Cognizant Agency (Agency Name, POC Name and Phone Number) IOHHS, Henry Williams, 214-767-3261
I
Indirect Cost Rate Agreement Date ~8/09/2006 I Total Indirect Costs I 117.500.0~
Modular Budget Page 16

TrackIng Number:
2011-04-22 000188
Principallnvestigator/Program Director (last, first, middle): POPUlIN, lUIS, C
PHS 398 Modular Budget, Periods 3 and 4

Budget Period: 3
Start Date: ~9/01/2009 I End Date: ~8/3112010 I
P". u,reCt ,-OStS Funds Requested ($)
* Direct Cost less Consortium F&A
I 250.000.0~
Consortium F&A I
I
* Total Direct Costs I 250.000.0~
B. Indirect Costs
1. IMDTC On-campus I ~ I 250.000_0~1 117.500.0~
2.
I I 0 I II I
3.
I I c=J I II I
4.
I I c=J I II I
Cognizant Agency (Agency Name, poe Name and Phone Number) IOHHS, Henry Williams, 214-767~3261 I
Indirect Cost Rate Agreement Date ~8/09/2006 I Tolallndirect Costs I 117.500.0~
Budget Period: 4
Start Date: ~9/01l201 0 I End Date: 108/3112011 I
* Direct Cost less Consortium F&A I 250.000.0~
Consortium F&A I I
B. Indirect Costs
Indirect Cost Type Rate (%) Base ($) * Funds Requested ($)
1. IMDTC On-campus
I~ I 250.000.0~ I 117.500.0~
2.
I 1c=J I II I
3.
I I c=J I II I
4.
I I c=J I II I
Cognizant Agency (Agency Name, POC Name and Phone Number) IDHHS, Henry Williams, 214-767-3261
I
Indirect Cost Rate Agreement Date ~8/09/2006 I

Total Indirect Costs I 117.500.0~

Tracking Number:
2011-04-22 000189
Principallnvestigator/Program Director (Last, first, middle): POPUlIN, LUIS, C
PHS 398 Modular Budget, Period 5and Cumulative

Budget Period: 5
Start Date: 109101/2011 I End Date: ~8/31/2012
I
* Qirect Cost less Consortium F&A
I 250.000.0~
Consortium F&A
I I
B. Indirect Costs
1. ~DTC On·campus
I~ I 250.000.0~ I 117.500.0~
2.
I I c::J I II I
3.
I I c::J I II I
4.
I I c::J I II I
Cognizant Agency (Agency Name. POC Name and Phone Number) jDHHS, HenlY Williams, 214-767-3261
I
Indirect Cost Rate Agreement Date ~8/09/2006 I Totallndirect Costs I 117.500.0~
I Cumulative Budget Information
1. Total Costs, Entire Project Period

I
* Section A. Total Direct Cost less Consortium F&A for Entire Project Period $1 1.250.000.0~
Section A, Total Consortium F&A for Entire Project Period $1 I
* Section A, Total Direct Costs for Entire Project Period $1 1.250.000.0~
* Section S, Total Indirect Costs for Entire Project Period $1 587.500.0~
* Section C, Tolal Direct and Indirect Costs (A+S) for Entire Project Period $1 1.837.500.0~
2. Budget Justifications
Personnel Justification EersonnelJustification1001742439.pdf I

Consortium Justification I I
Additional Narrative Justification I
I

Tracking Number:
2011-04-22 000190
Attachments
PersonnelJustification_altDataGroupO
File Name Mime Type
Person nelJustification 100 1742439. pdf application/pdf
ConsorliumJustification_altDataGroupO
File Name Mime Type
AdditionalNarrativeJustification_atlDataGroupO
File Name Mime Type

TrackIng Number:
2011-04-22 000191
BUDGET JUSTIFICATION
All categories are projected to increase by 3% each year. Fringe benefits are at the
projected University of Wisconsin rates.
Personnel ~ ~
Luis C Populin, P.h.D. FI~ PI, will devot 7.,{(.;t f his time to the project. /;fe will train
design and supervise e raining of the mon eys, perform surgical procedures to
implant eye coils and recording cylinders, perform the physiological recordings, analyze
the data and prepare manuscripts.
(, *. El:HlJAssociate Research Specialist, will devotei;!.Iff.'+~f her time

to the project.l. ]Sin charge of managing the primate colony of the PI's lab,
actively participates in the training of the monkeys, assists in the surgical procedures,
takes part in data analysis, and manages the overall functioning of the lab.
~,~ Programmer Analyst.) ''''Ji; <Buties are to maintain the

~i1n;o&c;recm[IDi;asd~rlt!Ee;ss.oftware analysis tools, and maintain all computer systems
as more than 20 years of experience in software development
and database !:re:::s"'ig:::n::-.-n:!e has built the lab's relational database for behavioral
(oculomotor) and electrophysiological data from the ground and interfaced it with the
analysis software tools.
"'~) Sr Information Processing Consultant.{_ ' '/k Jis a

L,,;""'c<1Cla=ls:niln;::"'e'""rto"'p;;:l;:;ng;:;-';;s:;:;o1ift;;:w~are applications that control hardware devices such as the
Tucker Davies Technoloaies ~ used in the PI laboratory for data acquisition and
stimulus presentationT ~as written and currently maintains and expands the
data acquisition software used in the PI's lab.
Post-Doctoral Fellow (100%): To be named. A post-doctoral fellow will be hired as soon

as the requested funds become available. Under the PI's guidance this person will be
responsible for planning, conducting, analyze the data, and publish the work. This
person will also be involved in the surgical procedures required to implant the monkeys
for experimental work, and will attend the Society for Neuroscience meeting to present
herlhis findings and learn about other work being done in the area of sensorimotor
integration.
Personnel Justification Page 20
2011-04-22 000192
OMS Number: 0925-0001

ExpIration Dale· 913012007
PHS 398 Research Plan
1. Application Type:
From SF 424 (R&R) Cover Page and PHS398 Checklist. The responses provided on these pages, regarding the type of application be-
ing submitted, are repeated for your reference, as you attach the appropriate sections of the research plan.
*Type of Application:
ONew • Resubmission o Renewal o Continuation o Revision
2. Research Plan Attachments:

Please attach applicable sections of the research plah, below.
1. Introduction to Application
(for RESUBMISSION,of REVISION only)
IlntroductionToApplication1001742536.pdf I
2. Specific Aims ~pecificAimsl 001742441.pdf J

3. Background and Significance ~ackgroundAndSignificance1001742436.pdf
4. Preliminary Studies I Progress Report

I
5. Research Design and Methods EesearchDesignAndMethodsl001742442.pdf
6. Inclusion Enrollment Report

I
7. Progress Report Publication List
I
fj!.!man Subjects S!1!;cljQ[l§:
Attachments 8-11 apply only when you have answered "yes" to the question "are human subjects involved" on the R&R Olher Project Information
Form. In this case, attachments 8-11 may be required, and you are encouraged to consult the Application guide instructions andlor the specific
Funding Opportunity Announcement to determine which sections must be submitted wi~h this application.
8. Protection of Human Subjects
9. Inclusion of Women and Minorities
10. Targeted/Planned Enrollment Table
11. Inclusion of Children
Other Researcb plan Sections
12. Vertebrate Animals ~ertebrateAnimals1001742435.pdf
13. Select Agent Research
14. Multiple PI Leadership
15. Consortium/Contractual Arrangemenls
16. Letters of Support
17. Resource Sharing Plan(s)
18. Appendix
List of Research Plan Attachments Page 21

Tracking Nu~ber:
2011-04-22 000193
Principal Investigator/Program Director (Last, first, middle): POPULlN, LUIS, C
Attachments
Introduction ToApplication_ attDataGroupO

File Name Mime Type
InlroduclionToApp/icalion1 0017 42536.pdf application/pdf
SpecificAims_attOataGroupO
File Name Mime Type
SpecificAims1001742441.pdf application/pdf
8ackgroundSignificance_attOataGroupO
FileName Mime Type
BackgroundAndSignificance1001742436.pdf application/pdf
ProgressReport_attOataGroupO
File Name Mime Type
ResearchOesignMethods_attOataGroupO
File Name MlmeTyp~
ResearchDesignAlldMethods1001742442.pdf application/pdf
InclusionEnrollmentReport_attOataGroupO
File Name Mime Type
ProgressReportPublicationList_attOataGroupO
File Name Mime Type
ProtectionOfHumanSubjects_attOataGroupO
FileName Mime Type
InclusionOfWomenAndMinorities_attOataGroupO
FileName Mime Type
TargetedPlannedEnrolimentTable_attOataGroupO
FileName Mime Type
InciuslonOfChiidren_attDataGroupO
FileName Mime Type
VertebrateAnlmals_attOataGroupO
FileName Mime Type
VertebraleAnimals1 0017 42435.pdf application/pdf
SelectAgentResearch_attOataGroupO
File Name Mime Type
MultiplePILeadershipPlan_attOataGroupO
File Name Mime Type
ConsortiumContractualArrangements_attDataGroupO
File Name Mime Type
LettersOfSupport_attOataGroupO
File Name Mime Type
ResourceSharingPlans_attOataGroupO
File Name Mime Type
List of Research Plan Attachments Page 22

Tracking Number:
2011-04-22 000194
PrincipallnvesUgatoriProgram Director (Last, first, middle): POPULlN, LUIS, C
Appendix
File Name Mime Type
list of Research Plan Atlachments Page 23

Tracking Number.
2011-04-22 000195
· \
2011-04-22 000196
Principallnvesligator/Program Director (last, first, middle): POPULIN, LUIS, C
A. SPECIFIC AIMS
The goal of this project is to extend our knowledge oHhe neural mechanisms that underlie the integra-
tion of information from different sensory modalities and their transformation into motor commands to gener-
ate gaze shifts. The experimental approach will be to record from single units in the intermediate layers of the
superior colliculus (SCi) of the head unrestrained (HU) monkey. Specifically, we will seek to define the relation-
ship between the magnitude and timing of sensory responses, motor discharges, and resulting gaze shifts.
Psychophysical studies have established that interactions among different sensory modalities have pro-
found influences upon perception and behavior. By comparison, much less is known about the neural mecha-
nisms underlying such interactions, which have been primarily studied in anesthetized animals. Much attention
has been focused on a process of non-linear summation of sensory responses called "bimodal enhancement"
that is readily observed in the SCi of anesthetized preparations. Bimodal enhancement is routinely cited in the
literature as the physiological explanation for behavioral facilitation.
Recent studies of bimodal integration in behaving animals have challenged the notion of bimodal en-
hancement as a mechanism underlying behavioral facilitation because large, enhanced interactions are not
Observed in behaving preparations (Populin and Yin, 2002; Bell et aI., 2001, 2005). Thus there is a large void
in our understanding of the neural mechanisms underlying the integration of sensory information from different
modalities and the behaviors they facilitate. The proposed experiments arose from the results of those carried
out in the behaving, head-restrained (HR) cat during the previous funding period, which cannot be adequately
addressed in the cat. The following four specific aims will guide the proposed work:
Specific Aim 1 will test the hypothesis that facilitation of behavioral responses to bimodal stimuli is medi-
ated by integrative mechanisms that obey linear (or sub-additive), not super-additive processes. Specifically,
this aim will investigatej- . -1Y . . ]'
C 0-
Specific Aim 2 will test the hypothesis that enhanced bimodal responses are observed in single SCi umts,
but under conditions of high behavioral significance to the subject. Specifically.,,! {
[ ? 7f=-
Specific Aim 3 will test the hypotheSiS that the SC operates in two distinct modes: a detection mode,
characterized by large neuronal responses that increase the likelihood of orienting movements directed to the
source of the stimUli, and an attention-driven mode, characterized by smaller, transient neuronal responses
that provide for further behavioral control- e.g., stopping the response if changing conditions so require. This
hypothesis arose from observations that showed that
Specifically, it is hypothesized that
Specific Aim 4 will test the motor error hypothesiS (Sparks, 1986) in the HU monkey. It is well established
that the representation of auditory space in the SC shifts as a function of eye position, but in HR preparations
the II : , Accordingly,
the motor error hypotheSis will be tested in the HU monkey using behavioral maneuver~l J
I ~ 1 ·
B. BACKGROUND AND SIGNIFICANCE

Interactions between different sensory modalities influence our perceptions and behaviors. They may affect
shifts of attention (Driver and Spence, 1998), sensory discrimination (Butter etal., 1989; Farahetal., 1989), and
reaction times (Frens etal., 1995; Taylor etal., 1999; Schrogerand Widman, 1998; Colonius and Arndt, 2001). A
great body of behavioral literature documents the psychophysics of this phenomenon, but relatively little is known
about the underlying physiological mechanisms. Thus, there is a large void in our understanding of the neural
mechanisms that govern behavior in normal, everyday multisensory settings. In fact most of what is known has
been learned from the superior colliculus (SC) of anesthetized preparations.
The SC has served as the model for the study of multisensory interactions. It receives ascending and de-
Specific Aims Page 27
2011-04-22 000197
Principallnvestigator/Program Director (Last. first, middle): POPULlN, lUIS, C
scending sensory inputs (Huerta and Halting, 1984) where they form representations of visual (Stein et aI., 1976;
Finlayetal., 1978) and auditory (Gordon, 1973; King and Palmer, 1983; Wise and Irvine, 1983; Middlebrooks
and Knudsen, 1984; Hirsch et aI., 1985) space, and body surface (Cynader and Berman, 1972; Meredith et aI.,
1991), The SC is also the site of various motor maps that underlie eye movements (Robinson, 1972; Schiller and
Stryker, 1972; Guillon etal., 1980) and pinna movements (Stein and Clamann, 1981).
In anesthetized animals, the various maps are in spatial register (Gordon, 1973; Stein et aI., 1976; King and
Palmer, 1983,1985; Meredith and Stein, 1986a,b), a phenomenon thought to be a manifestation of a fundamen-
tal aspect of SC organization and function (Stein and Meredith, 1993). In behaving animals that move their eyes
relative to their heads, the maps can be brought out of register (Poppel, 1973), Thus the alignment is thought
to be actively maintained to compensate for eye movements (Jay and Sparks, 1987b; Populin et al., 2004). Our
understanding of the principles that govern multisensory interactions under such dynamic conditions, and the
transformations that lead to behavioral facilitation, is rudimentary at best. Thus, a fundamental goal of the pro-
posed experiments is to contribute to our understanding of this area.
Bimodal interactions in the intermediate layers of the superior colliculus
Studies by Stein and colleagues in anesthetized animals have shown that information from different sensory
modalities is integrated non-linearly by neurons in the SCi, which results in bimodal enhancement (or suppres-
sion) of sensory responses (Meredith and Stein, 1983; King and Palmer, 1985). Bimodal enhancement is thought
to be a mechanism that facilitates the detection of biologically relevant stimuli and the subsequent orientation
to the sources (Meredith and Stein, 1983; 1986a,b; Newman and Hartline, 1981; King and Palmer, 1985; Stein
and Meredith, 1993). It is is frequently cited in the psychophysical and functional imaging literature as the physi-
ological explanation for the well-documented facilitation of behavioral responses to bimodal stimuli (Calvert,
2001; Calvert et aI., 2000, 2001; Driver and Spence, 1998). Interestingly, summation of sensory responses of
the magnitude reported in anesthetized animals, which can reach up to 300% in the anesthetized cat (Meredith
and Stein, 1986b) and 452% in the anesthetized guinea pig (King and Palmer, 1985), has not been observed in
behaving animals (Populin and Yin, 2002; see also the data by Bell et aI., 2001; 2005).
Populin and Yin (2002) tested for the presence of non-linear interactions of sensory responses in the SCi of
behaving cats trained on audiooculomotor tasks. They hypothesized that if bimodal enhancement, which is so
prominently observed in anesthetized animals were a mechanism underlying behavioral facilitation, it should be
readily observed in a behaving preparation that actually shows behavioral facilitation to bimodal stimuli.
The responses to bimodal stimuli recorded in the SCi of the behaving cat were larger than the responses to
either single modality stimulus but were ,
Auditory Bimodal
slightly smaller than their sum, in many
. t h' I'
inS ances approac Ing Inear a lion" 0>
dd·t'
(Populin and Yin, 2002). Fig, 1 illustrates ~~ 0
Visual
saccade latency:
.88.3 msec (SO"48.9)
!rpA L
saccadelaten<y:
Em.
=: I
msec(SI>.±95.4)
;~L
an example from the population studied :!!! ·20 8. ~ [7:.:J ~ .
by Populin and Yin (2002). The saccadic :"0" 12 1' . "'J',""""""""."'.. ".. 1 . If""'"'' "Y....·',',
eye movements executed by the cat to i" 2.5 . ..... ) &(:<:;'.I,)ii,(;\~"~
I I
,11;; ....· ·
bimodal targets during those recordings
were more stereotyped and consistent
E 1)
~ 'g.
I
00 .
I
WIi", ." ,. c-_-!,"'''......OJI.~.wjI''''.....J,/U
..''''"....
than those to visual and acoustic targets, ',500 0 500 1,000
and most importantly, they had a shorter Time (ms)
latency: that is, they were facilitated, The Fig 1. Bimodal neuron in the SC of the cat recorded with fixation
single unit responded to both visual and task. Top, vertical component of eye movements to targets at (0,-
acoustic stimuli. The bimodal responses 23) deg. The visual stimulus was a red LED, the acoustic stimulus
were 7.5% larger than the sum of the two was broadband noise, and the bimodal stimulus was a combined
unimodal responses, indicating that they visua/~acoustic presented sim~ltaneou~/y f~om the s~"!le location.
were not enhanced. These bimodal data, BehaVIOral responses to the bimodal stimuli were facilitated.
which are in stark contrast with those from the SC of anesthetized cats, are representative of the integration pro-
cesses in the SC of the behaving cat (Populin and Yin, 2002). Note: similar results, albeit interpreted differently,
have been published by Bell et al. (2001).
Bell et al. (2001) hypothesized that the lack of large bimodal enhancement in their recordings was perhaps
due to the fact that the RFs of most of the neurons they studied covered the central portion of space. They sug-
gested that bimodal enhancement might be more relevant and important for processing stimuli located farther
away from the fovea, as suggested by Anastasio et al. (2000). The argument is that in more peripheral areas of
Background & Significance Page 29
2011-04-22 000198
space, where latencies to visual stimuli are longer and thresholds for detection higher, there is room for auditory
stimuli to contribute, resulting in facilitation of behavioral responses. Thus, behavioral facilitationjnJhe_perinhF!rv
Js attributed to bimodal enhancement. Gaze latencv data from our laboratorv. however suggest'
YJ:
.. . .. ..
ranger latenCies are Indicative of Increased tasK dlTTICU IV lr osner,

1978), thus it is assumed thatl
~
Studies of bimodal inte gration in monkeys (Bell et aI., 2UU'I, LUUO; Frens and Van 0 pstal, 1998) and humans
(e.g., Colonius and Arndt, 2003) have required subjects to orient to the visual component of the stimuli and to
ignore the acoustic. Under these conditions the acoustic stimulus is used as either a distractor or an attractor,
depending on the degree of spatial congruency. Thus, is it really important to require subjects to treat the sources
of acoustic stimuli as targets for saccadic eye movements? Is it relevant and why?
We believe that the answer to these questions is yes because primates can actually orient to the sources of
acoustic stimuli (Populin, 2006) - there is no reason to assume that primates do not treat acoustic stimuli as tar-
gets for saccades. Therefore, considering the acoustic component of bimodal stimuli, as well as acoustic stimuli
as non-tar ets should lead to an incorrect model of bimodal inte ration.
*
t is POSSI e a me 0 0 ogical dl icu ties may have contribu e to t e approac 0 not requiring subjects
to treat sources of acoustic stimuli as targets for saccadic eye movements because measuring gaze shifts to
acoustic targets is not a straight forward process, neither in humans nor monkeys. In addition, it has been report-
ed that monkeys are difficult (if not impossible) to train to perform saccadic eye movements to acoustic targets
(Grunewald et aI., 1999; Linden et aI., 1999). The experiments proposed in Aim 1 will not be constrained by this
limitation because monkeys are able to orient to acoustic targets (Populin, 2006).
It is our contention that the kev to understanding how facilitation of behavioral responses to bimodal stimlllL
is brought about resides iriJ
t:.TTeCtS OJ higher order variables on ;:'1,; Junction

Bimodal integration has been defined by temporal and spatial interactions between ascending and descend-
ing sensory inputs (Meredith and Stein, 1986a; Meredith etal.,1987; Stein and Meredith, 1993; Wallace and
Stein, 1994). As discussed above, there are large discrepancies in the magnitude of bimodal integration indices
between anesthetized and behaving preparations. Studies in anesthetized animals report increases in the mag-
2011-04-22 000199
Principallnvestigalor/Program Director (Last, firs!, middle): POPULlN, LUIS, C
nitude of responses to bimodal stimuli as large as 300% (Meredith and Stein, 1983), and in some cases up to
infinity (Meredith and Stein, 1986b). On the other hand, studies in behaving animals that used the same index
to quantify bimodal responses report changes that ranged between 25-66% (Bell et aI., 2001). Differences just
as large were reported by King and Palmer (1985) from anesthetized guinea pigs and by Populin and Yin (2002)
from behaving cats that used the same metric to quantify bimodal interactions.
However, Bell et al. (2003) have suggested that higher order variables, not just the intensity, spatial, and
temporal properties of the stimuli, might be responsible for the differences in the magnitude of the integration
indexes observed between the anesthetized and behaving preparations (see Corneil and Munoz, 1996; Munoz
and Corneil, 1995). With the exception of Bell et al.'s (2003) findings in the monkey that the act of fixation, not
just the mere presence of a fixation light, can influence sensory responsiveness and bimodal integration, we are
not aware of any other physiological s!udy in which higher order variables, representing cognitive aspects of an
experimental task, have been included in the design of the experiments. The SC of cat (Harting et al., 1992) and
monkey (Huerta and Harting, 1984) receives numerous descending inputs from the cerebral cortex that could
convey signals representing the hypothesized higher order variables to the SC.
Tests of the effects of instructions on bimodal integration, e.g., maintain fixation versus make a saccade, or
higher order variables pertaining to the significance of the stimuli, e.g., the size of the reward, must be carried
{Jut on the same neurons of the same animal using identical sensory stimulation. Accordingly, Aim 2 will test the
hvpothesis thall
Monkeys are very sensitive to these types or mampUialions Wiatt and Glimcher, 1999).
In addition, the experiments proposed in Aim 2 will provide an important control for the experiments pro-
posed under Aim 1. A common problem encountered in experiments with behaving animals is that subjects do
not respond in trials in which stimuli are presented at near threshold levels (Frens and Van Opstal, 1998), which
is paradoxical because bimodal integration mechanisms, according to the law of inverse effectiveness (Stein and
Meredith, 1993), are expected to compensate for the poor effectiveness of low intensity stimuli by non-linearly
enhancing the magnitude of the In "".,.,.,.,<on Ihaexp·· work prollOJled J.lnd~r Aim 2 will test
the hypothesis tlJatr
The role of suppressive interactions in defining SC function

The results of our studies of bimodal integration in the behaving cat revealed (1) lack of large bimodal en-
hancement and (2) prominent depressive effects. The depressive effects were readily observed when the subjects
were required to fixate a visual stimulus, and were ubiquitous throughout the SCi. The question arises, therefo
as to the functional si nificance of these depressive interactions. We hypothesize tha
We further hypothesize that!
a ground & Significance Page 31
2011-04-22 000200
Principallnvestigator/Program Director (last, first, middle): POPULIN, LUIS. C
~ b~
_ _~;'\S'Iml'I ar 0 serva-
':lIons nave been made by Bell et al. (2003) in the monkey and
/
by Rizzolatti et al. (1974) in the paralYZe. d c.at using visual
~~muli. Figure 3C sho~I r
I
~ ~I
\ \Thelmplementation of this hypothetical
~echanLsm in the SCi coulp rely on c= _~_____ i .. - ~~..J
I-.~_ _ _~-",{k,,--_ _ol This type of mechanism, i.e., I - ~) has
been demonstrated in the superficial gray layer (Pasternack et aI., (1999).
In summary, while it is very clear that responses to stimuli presented within a un. it's best area are SignifiCantly]
?hanged, it remains to _~e determined ifRFs are affecte~ a?d how. S _ . ~ _
h-LE!1e experimental work proposed under Specific Aim 3 is designed to answer this question.
\=-- . -
1 J W~ predict that ! .
Aim 3 will support our hypothesis tnat)
~ '0 be carried out
- /;
i~
[ - .~ .I
Suppressiv.e interactions: basis for implementation of motor error \
,- and eye head coordination . \
It is well established that SCi neurons respond maximally to a stimulus >---------......__--.J
presented within their RFs in the absence of other stimUli or behavioral Fig 4. Hypothesized forms of
constraints. The mere presence of a second stimulus anywhere in the ip- receptive field mOdulation.
silateral or contralateral hemifield (Populin and Yin, 2002; Rizzolatti et aI.,
1974), or the act of fixation (Bell et aI., 2003), invariably reduce the magnitude of responses to sensory stimuli
(see Fig. 3). The large difference in the type of responses to identical stimuli led us to hypothesize that the SC
operates in two distinct modes: detection and attention (Specific Aim 3).
Invariably, modulation of sensory responses in the SCi takes the form of a reduction of the lar er res onses
recorded in the detection mode. Thus, the evidence from behaving preparations suggests tha.!l-
\ .:::~
Acute experiments in the SC revealed that sensory stimuli of different modalities presented from a given
area of space activated the same part of the SC, suggesting that the various maps are in spatial register.
The alignment of the maps, therefore, was thought to provide the neural substrate for sensorimotor integration
""k ~rOr( ~ +~iO-tlVY>~

2011-04-22 000201
Principallnvestigator/Program Director (last, first, middle); POPUlIN, LUIS, C
(Gaither and Stein, 1979; Gordon, 1973; Harris et aI., 1980; Stein and Meredith, 1993). However, as pOinted
out by Poppel (1973), because the coordinate systems for vision and audition are different, with the visual map
oculocentric and the auditory map head-centered, the alignment hypothesis holds only when the two represen-
tations are in register, i.e., when the eyes and the head point in the same direction (Gordon, 1973; King and
Palmer, 1983; Meredith and Stein, 1985; Middlebrooks and Knudsen, 1984; Stein and Clamann, 1981; Stein
and Meredith, 1993). Thus in behaving subjects whose eyes are free to move, one would expect the maps to
become misaligned whenever the eyes are not at the straight ahead position. For primates, who move their eyes
-3 times per second (Albano et aI., 1982; Schiller et aI., 1980), misalignment of the maps should be practically
the constant condition.
)
..?enavloral tests indicate that this is clearly not the case. Regardless
'roinre'l'irr7io:Flrsr;,mflin;:;;atf'ri'<e><:sITu"It'II,fI'VII'''' ,,,,,tn,,,c:nIl'TT""jin""n~-tI""ms-",~mead, saccadic eye movements of cats and monkeys to sound sou rces
i'I' ""n,"""
do not show a systematic effect of initial eye position (Populin, 2003, 2006; Populin et aI., 2004), suggesting that
some type of compensation is implemented.
It has been suggested that the representation of auditory space in the SCi shifts to compensate for changes
in eye position in order to maintain the alignment between the auditory and visual maps. This mechanism yields a
representation of motor error, which is the difference between eye position and the target. In this scheme, known
as the "motor error hypothesis" (Sparks, 1986), the shifted auditory representation of space does not encode
the position of acoustic targets relative to the head, but rather their location relative to the position of the eyes
within the orbit. Recordings from monkeys demonstrated that the representation of auditory space in the SC of
this species shifts as a function of eye position Jay and Sparks, 1987b). In the cat, on the other hand, conflicting
evidence had been presented. Harris et al. (1980) reported that the auditory representation of space did not shift,
while Hartline et al. (1995) and Peck et al. (1995) reported that it did. The cat presents a different set of conditions
than the primate due to its limited oculomotor range. The combination of a limited oculomotor range (- ±20 deg)
and large RFs of SCi neurons should not require shifts to maintain alignment because the eye movements are
not large enough to cause misalignment (Harris et ai., 1980; Stein and Meredith, 1993).
However, the interpretation of the results from the cat studies was hindered by methodological problems
such as limited sample size, untrained and inconsistent subjects, and inadequate monitoring of eye and ear posi-
tion. Populin et al. (2004) carried out a study designed to overcome those difficulties using cats trained to localize
sounds and well-controlled experimental conditions. That study demonstrated that the auditory representation of
space in the SC of the cat Shifted with eye position as in the monkey. The magnitude of the shift of the auditory
map, 54% in the monkey and -63% in the cat, was comparable in the two species, but incomplete, i.e., not pro-
portional to the deviation of the eyes from the straight-ahead position. Thus, although it is clear that the auditory
map in the SC shifts, the magnitude of the shift does not match the predictions of the motor error hypothesis. Jay
and Sparks (1987b) suggested that (1) incomplete sampling of the horizontal aspect of the RFs, coupled to the
fact that the vertical component was not sampled at all, or (2) a gradual transition from sensory signals to motor
error signals in'the SC might account for the incomplete shifts of auditory RFs found in their data.
The fact that cats and monkeys orient inaccurately to sound sources when their heads are restrained, invari-
ably undershootinQ their taraets (Populin, 2003; Populin and Yin 1998; Tollin et aI., 2005), suggests two other
possibilities. First,1 ~L l
--1f- i It IS well documented that the
muscles of the neCK or animals tnat nave trained w neadS restrained for many months and vears continue
/Second, the alternative hypothesis _
I
hy~othesis: (1 U.
r
Two indirect lines of evidence support the se_cond
2011-04-22 000202
Principallnvesligator/Program Director (last, first, middle): POPUUN, LUIS, C
The results of Bizzi et al. (1972) demonstrate that behavioral context has a significant effect on eye-head co-
ordination. In that study, when monkevs could not predict the time of onset of a visual tamet, gaze shifts started
will1 the eves followed bvJhe headJ . !
I ~
*
L--=-=-z=::-::nc.:-;=-=:-:'~Jthe gremesl senslllvllY Tor OIscnmmalion is in the area of frontal space (Blauer, 1983)
- as defined by the interaural axis.
}measured a"
in Freed an tioarKS (1997a).j
D. RESEARCH DESIGN AND METHODS

The proposed work makes use of a new HU monkey preparation (Populin, 2006). The rationale for changing
from the HR cat to the HU monkey is the following: 1) The study of how motor commands are generated based on
sensory inputs requires a preparation in which sensory and motor-related neural activity can be readily recorded.
While the se of the HR cat is a fruitful substrate for the study of sensory responses (Populin, 2005; Populin and
Yin, 2002; Populin et aI., 2004), motor activity is difficult to find - we have found eye movement related activity
in -5% of the hundreds of neurons we have studied in the Sei of the HR cat. In the se of the monkey, on the
other hand, sensory and motor responses are readily found; this is essential for Aims 1 and 4. 2) The monkey
is capable of performing complex tasks with a high degree of cognitive content, which is necessary for Aims
2 and 3. 3) The study of the mechanisms in the se that generate gaze shifts will be facilitated in the monkey
because movements of the eyes and head are much more independent than in the cat; this is vital for Aim 4. In
addition, the cat has a very limited oculomotor range, thus under HR conditions the best areas of many auditory
Research Design & Methods Page 34
-¥ \?ropr~ ~{or nY\~

2011-04-22 000203
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neurons are beyond the reach of eye movements; thus no functional relation can be established between neural
responses and behavior. 4) Among the available preparations for studies of this type, the monkey is the closest
to humans, including the psychophysics and kinematics of orienting.
Subjects and preparation. The subjects will be 12 male rhesus monkeys. Each monkey will undergo one sur-
'" gery to implant a head post, eye coils, and a recording chamber; additional surgeries may be needed to replace
~ ~ broken eye coils. The head post will be used to restrain the head to care for the wound-edge around the implant
'i1" and during the initial training, and to hold the spouts used to deliver liquid rewards in the HU condition. The
. \::' ~ periosteum inside the recording chamber will be removed and the bone covered with acrylic. Eye coils, made of
I:::.. I lvire (Cooner Wire Co, Chatsworth, CAl will be implanted as described Judge et al. (1980). The head coil,
( of similar construction to those used for the eyes, will be implanted in the head cap.
Experimental sessions. A typical experimental session provides 2-4 hours of recording time, during which the
subject performs -3500 trials, with occasional sessions of up to 5 hours, producing> 5000 trials. The large num-
ber of trials we obtain from our monkeys is essential for the proposed experiments, particularly those under Aim
3, which require extensive RF mapping. In the HR cat, where we succeeded in mapping auditory RFs (Populin
et aI., 2004), we were able to obtain only -500 trials or less per recording session.
Experimental setup and stimuli presentation. The experiments will be done in a 3x3.7x2 m double walled
sound chamber (Acoustic Systems, Austin, TX); the interior of the chamber and all major pieces of eqUipment in
it are covered with reticulated foam (ilibrook, Minneapolis, MN) to attenuate acoustic reflections. Acoustic stimuli
will be generated with Tucker Davis Technologies System 3 (Alachua, FL) hardware and presented through any
of 32 speakers (MDT-20, 28 mm, Morel Acoustics, Brookline, MA) that can be positioned anywhere around the
subject, 84 cm from the center of the head. Visual stimuli will be LEOs attached to the front of the speakers.
Eye/head movement recordings. Eye and head movements will be measured with the search coil technique
(Robinson, 1963) using a phase angle system (CNC Engineering, Seattle, WA), the horizontal output of which
is linear over a 270 deg range. The eye coils will be calibrated with a behavioral procedure that relies on the
animal's tendency to look at spots of light presented in a dimly lit or dark environment. To calibrate the head coil a
laser pointer will be attached to the head post, and the investigator will manually align the laser beam with LEOs
at known positions by moving the monkey's head. Linear functions will be fit to the output of the coil system to
transform voltage to degrees of visual angle (Populin, 2006). Horizontal and vertical eye and head position sig-
nals will be digitally sampled at 500 Hz with an analog-to-digitalconverter (Tucker Davis Technologies, Alachua,
FL) after analog low-pass filtering at 250 Hz (Krohn-Hite, Brocton, MA).
Physiological Recordings, criteria for SCi recordings, and receptive and motor field mapping. Single unit
recordings will be obtained with 1-2 MOhms tungsten electrodes (MicroProbe, Potomac, MD). Small holes will
be drilled through the acrylic and skull inside the recording chamber to insert electrodes into the brain inside
guide tubes with a Narishige MO-95 microdrive (Narishive, International, East Meadow, NY). A grid attached to
th(J recording chamber will guide the insertion of the guide tube. We have adopted this approach, for which we
received extensive guidance from Drs~ -i= land discontinued the traditional craniotomy
because (1) the dura matter does not arden over time, (2) recording stability is better, and (3) no surgery to
implant the chamber is needed after training when the subject is performing at its best, which imposes a period
of recovery. The neural signals will be amplified (Bak Electronics, Mount Airy, MD) and bandpass filtered (0.3-3
KHz; Krohn-Hite Co, Brockton, MA). Pulses generated by a window discriminator (Tucker Davis Technologies,
Alachua, FL) when action potentials meet the criteria set by the investigator will be recorded with an event timer
with jJsec accuracy and saved on disk for analysis.
The first recordings in each animal will be made with the HR to determining the orientation of the grid used to
guide the electrodes into the brain with respect to the visual map in the superficial layers of the SC (Cynader and
Begman, 1972). Typically, after 3-4 successful electrode penetrations it is possible to predict the location of the
RFs in future electrode penetrations. After the relation between the orientation of the grid.and the visual map of
the superficial layers is established, the head of the anim I will e sed before lowering the electrode into the
Ci. As the animal e s arious ex erimental tasks PY"l'yl~0 fr.-f.o
e WI est our pre IC Ions
'-:a:::ib::-:o~u:rt1It:::e~l-::::oc:::a"'t~1o:-::::n""o:Ti1t::-:e::-:::ier.:e-;:'ctr:ro;:;:r;e::-ir:::n:-ithhe;::-;::co~Ii1t1c;;;u""a"'r'"'m"'a"'p;;-.-m"'e~W"'I"""'re""yC;-;::o:::n~p:;::h:-:ys:::io::;l;:::o-:::gI;:::'c::::faI crite ri a to d ete rm ine if th e
tip of the electrode has reached the SCi: (1) recording depth relative to the start of the strong visual activity of the
superficial layers (-1-15 mm), (2) the presence of auditory responses, 3) motor discharges associated with eyel
gaze movements (Sparks, 1986, Wurtz and Goldberg, 1972). If the pattern of physiological responses does not
conform to our expectations we will restrain the head of the animal and re-test; if needed we will reposition the
2011-04-22 000204
Principallnvestigator/Program Director (Last, first, middle): POPUlIN, LUIS, C
electrode. We will not attempt to isolate single units until we are certain that the tip of electrode is in the SCi.
Neuron Classification. Once the decision is made to study a neuron, the first task will be to determine its
type; eventually, as the number of neurons studied grows, we will have to select neurons based on their proper-
ties. SCi neurons will be ciassified in three categories: sensory, motor, and sensorimotor neurons. Sensory neu-
rons are those that discharge in response to the presentation of visual andlor auditory stimuli, and do not show
motor-related activity, i.e., do not discharge before gaze shifts. Motor neurons are those that do not discharge
to the presentation of sensory stimuli, but discharge before/during gaze shifts. Sensorimotor neurons are those
that respond to the presentation of sensory stimuli and discharge in relation to gaze shifts. Further sub-classifica-
tions may turn out to be necessary to accommodate neurons that may respond to stimuli from only one modality
but are influenced by the presence of stimuli from another modality that when presented alone does not evoke
a response (Populin and Yin, 2002; Populin et aI., 2004 ).J
/
-
:i:-
. JIO objectivelY aetermlne the presence Of motor activity the motor Inaex usea oy
Freedman and ~rks (1997b) will be used.
- - -
-
-t"
- 3
Movement fields, the range of saccade (gaze shifts) directions and amplitudes that are precededlllLa ourst
_~fllJ;tivi!y'_(Sparks and MaY~.1illill)..will he comouted for eveN neuron that exhibits motor discharaesl ..
*:
. et aI., 20050 . . . *
Tne onset of a burst of activity associated with a g aze shm Will be defined as tne lime at wnlcn me linn
exceeds 40 s~es/sec and the offset as the time at which the discharge rate fall below 40 spikes/sec
er e ermlnlng a neuron s ype, I WI e asslgne 0 e mos SUitable experiment in any of the Aims;
rate
the exception will be Aim 2, which requires specific training. Sensory neurons will be suited for Alms 1 and 3;
those with circumscribed RFs will be best suited for Aim 3. Neurons with motor-related discharges will be ideal
for Aims 1 and 4. Our data acquisition software allows us to tailor an experimental session withoutsto the
monke 's work ~
.'
ypically, neural thresholds are lower than behavioral thresholds. This may present a
'-=p""ro=e"'m=""o-=-r"'str.-u::Jdi:':yr::in:::g:-:n::-:e:7u~rons at low enough levels to facilitate multisensory interactions because animals tend
not to respond at low levels of stimulation (e.g., Frens and Van Opstal, 1998).
Behavioral training: general. Behavioral training is based on positive reinforcement. Monkeys are fit with a
collar and taught to accept being handled with a pole and to enter a primate chair before the first surgery. Once
implanted with eye coils and a head post, the monkey is placed in the recording room to obtain calibration co-
efficients for his eye coils. This is accomplished with the visual form of the fixation task with the HR. After the
coefficients are obtained, the auditory version of the fixation task is introduced. We use these tasks to teach our
subjects the basics of our paradigm: orienting to the source of a stimulus leads to a reward (Populin, 2j2QJ,~0,-,6..l=-._ _-,
After the animal has made the connection n orientina and to a tamet an receiving a reward
-¥ 9r6pl"~ --:r;;~Olf1'n~
2011-04-22 000205
Principallnvesligator/Program Director (Last, first, middle): POPULlN, LUIS, C
L~~~~~*~~~~~J
Histology: electrode tract location. At the end of the recording life of each animal electrolytic lesions (e.g.,
30-IJA anodal current for 30-45 sec) will be made in selected locations to help reconstruct electrode tracts. The
placement of the electrodes will be carried out under the guidance of the grid. We will also have the opportunity
to place our monkeys in an MRI located at the Waisman Center of the U of Wisconsin to obtain anatomical infor-
mation with the tungsten electrodes in place; we will follow the procedures described in Metzger et al. (2006).
Specific Aim 1
This Aim will test the hypothesis that behavioral facilitation of responses to bimodal stimuli results from lin-
e~ (or sub-additive), no!..§..upper-additive i~[Qtive mechanisms. It is further proposed tha!i'-~~-~-----l
Ex eriment 1. The roposed wor or 1m IS I us ra e In I 1. 1
Sensory data from the cat provide preliminary support for his Aimi~':...:Fi,-"g_1:..o3~s",h-,-,0c:.w,-t:;.;hc::el.-_ _ _ _ _ _==,~
latency (unpublished data from three HU cats from this lab) and the
average magnitude of all sensory responses recorded by Populin
and Yin (2002) from the SC of four different HR cats. The behavior
data from Po ulin and Yin 2002
e SIS WI e ana yze using a velocity criterion to determine the onset, offset. peak velocity. and other
kinematics parameters (Populin, 2006) using custom software. The results will be stored in a relational database
for further_an~lysis: Physiological data will be analyzed as follows
;k 9rorr~ ~~orrm~
2011-04-22 000206
Principallnvestigator/Program Director (last, first, middle): POPUUN, lUIS, C
l~------,~----,---,----~\
f...... Tfie onset of a burst of activity
h;a~s"'so"'cqlaar.s""w"lffn"a"g"'a=,-"ji'rlft-itM"'ei7foe""'m;;;e;;t as the time at which the firing
rate exceeds 40 spikes/sec and the offset as the time at which the discharge
rate fall below 40 spikes/sec (Takeichi et aI., 2005). Many burst SC neurons
exhibit little spontaneous discharge (Jay and Sparks, 1987a) thus detect-
ing their onseUoffset should not present problems'
>k-
e mde endent varia Ie will be the t e of stimuli - visual, acoustic'
an
~ between the behavioral and neural variables wll

he relation
e e regression analysis (,General
IL.J.)'~_ _ _ _ _ _ _ _~_------_ _-c-,
Linear Model') in SPSS v14.0 (SPSS, In.-",c;-:;C""h,!!i~ca;!\gl"o,,-,...
Additional considerations for anal sis ~ I
'-]~timJ.V1Oinh~~mn~~~~~um~(HaGITmnn~TIT~TInmm~rr}.T~hAe"S~e~n~so~~~d~a~ta~rr~o~nl~t~h~e~cva~t~shh~ow~t~h~at~
esponses are preserved in the bimodal
er 0 su Jec s an neurons 0 e num e

#c- les as well
as the number of animals used for obtaining them varies considerably (e.g., Freedman and Sparks, 1997; Gold-
berg and Wurtz, 1972a; Mays and Sparks, 1980). Based on those numbers; which range from -35-380 neurons
from 2-7 animals, we estimate having to record from a total of -125-175 neurons, a number that will require 3
monkeys. Eve~ effort will be made to obtain equivalent samples for each of the major types of neurons targeted
(senso~, motor, and sensorimotor). We further estimate that completing Aim 1 will require approximately 1.5-2
years of experiments. Assuming that we start with na'ive monkeys, the first subject will be ready for recordings in
approximately 6-9 months. Once recordings start, we anticipate recording from each subject for -3 months. Un-
der the PI's supervision the lab technician trains 3 monkeys per day. This is illustrated in the TIMELINE below.
Potential Problems and Interpretation of Results, 1) We may encounter 'large differences in the threshold
(responsiveness) of senso~ neurons, which are typically lower in SC neurons than behavioral thresholds. A
common problem with behaving animals is that subjects do not respond in trials in which stimuli are presented
at near threshold levels (Frens and Van Opstal, 1998), which is paradoxical because bimodal integration mecha-
nisms, according to the law of inverse effectiveness (Stein and Meredith, 1993), are expected to compensate for
the poor effectiveness of low intenSity stimuli by non-linearly enhanCing the magnitude of the senso~ responses
r
th<?~\l~t to drive the behavior. Because this Aim will test the hypothesis that th~~~'~"''--''--'"''~''''''''' "'".
.1,/,'
if!:
2 We hypothesize tha
~ c?ro(iJ~~ -l-1\~OI ('O')~

2011-04-22 000207
Principallnvestigator/Program Director (last, first, middle): POPUUN, lUIS, C
-~ -
~---~--------~-
- .,' .
~
t
[~
~ I ~ue to tile
1986), we optimistically anticipate being able to
-
fr-
close associa,iull u",ween t~s= Ical aCllVI!y 0 ne S(; and orientinq behavior (Sparks,
~
The major question, therefore, will concen~ the validitY of the proposed mode!.1
- -- --
scheme. The eXisting data, however, suggest that this will not be the case.
Specific Aim 2
*
)NiII call for rejection of the proposed hypothesis and for reconsideration of the entire
While there is evidence showing that enhancement of sensory signals (large non-linear summation) by SCi
,
neurons is the result of spurious effects of anesthetics (Populin, 2005), experiments in behaving animals, which
do not show enhancement, have not considered some potentially important higher order variables. Specifically,
such studies have attributed the same behavioral significance to both unimodal and bimodal stimuli: that is, ori~
enting to the source of either type of stimuli led to the same reward. This may actually not be the case in nature,
where concurrently seeing and hearing information arising from a single event or object leads to improved be-
havioral performance and, thus, increases the changes of success (e.g., obtaining a meal or avoid becoming a
meal). In other words, the process of integration, in the SC mav not necessarily be restricted to sensory signals.
Accordingly, this Aim will test the hypothesis that enhanced bimodal responses will be observed in SCi units, but,
under conditions of high behavioral significance. The two experiments that comprise this Aim will require specific'
- training. Thus, subjects, two per experiment, will be assigned to only one. The need for the second experiment
will be contingent upon obtaining a positive re~!JIt,=,f,!dro~m.::...:t:.:he:::...::fi:::rs::.:t:...~----"""-===="""'=----1
.-__.cE=xc£P,eriment 2.1. This experiment will lest!
IWO ti'Jles of control trials are. bUllllnttlis experiment (but aJso see Exp. 2.2 belOW). First, the results ot the
¥ will "en'e as contl'Ols, to be compared against
L.,...,=====","":::-iJAllernativeIY, IT expectation IS wnat matters regarOiess OT type or stimUli, me responses to

-unlmooal stimuli in the 20% of cued trials should change. SecondL *-
h b-":im;;:o;:;d""a:rI';:re"'s"'p"'o""n""se;;-r.ln'"'t'"h:::e::::se:::-
..::tc 'he ;;m::::a::::g""n"'itu=dEeC-:o;;1f"tt'he
~ trials should approachltre'§um of Ille tWO Unimodal responses (Populin and Yin, 2002),[£ ---,
_
~* ]we anticipate that -6 months of train-
¥ (?foPt~ TI\\Of~
2011-04-22 000208
Principallnvestigator/Program Director (Last, first, middle): POPUlIN, LUIS, C .
ing will be needed to prepare the monkeys for electrophysiological recordings, which should take -2-3 months
in each monkey. The start of the training of the monkeys will start with a -3 months separation in order to have
the second monkey ready at the about the electrophysiological recordings in the first are completed. Thus, the
experiment should take about 1-1.25 years to complete.
Ex erimental tasks and stimuli. As stated above, the experimental tasks will b{ ';K
~-'--'-'=::::lr_ _ _-'~~_ _ _ _ft:=-='lffittlHor-these-eX\3eFimeRts will be the s';am;:;:;;;e~t;;o~thh"os";e;;':_Tlu~se"'d.rhfo"'r'"'Arol"m;--
at is, ' > k ---.-Jl'he consid-
erations discussed above in terms of level also app y to t ese experlmenc:rs~._ _ _~
Physiological recordings and analysis. This ex eriment will focus 0
he data will be analyzed using Multip e Inear egression enera Inear Mode!') in SPSS
J
~V1:r4'--."07S""pns~s-,I{~nc. Chicago, IL). In general, the approach for tl:ie-aoolysis will be tile sallie as iR Aim 1 but the .
emphasis will be placed onl - 1
--'--- f' n e pas we a ply computed all index to deteFmiR6-if-the-"
1m .. _, . ::-:.-.nse excee e e sum 0 t e single modality responses (Populin and ';in, 2002). However, such
analysis did not allow us to take into account the behavioral responses. In this casey *-
L
1
The results trom Aim 1 will be used as a oencnmarK. In addilionJ
.. . ~
If-.
/(\
For the controls built in tms expenment, wnlcn Will serve' as 1n00cators a's to whether or notto proceed with
Experiment 2.2., comparisons will be made between trialsl
~I
'--_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ )tis hypothesized thatl'L,.·"_ _ _ __
J
Elgleriment 2.2. This is a control for Experiment 2.1. This exp~riment is aimed at I
..
Two
monkeys will be used. Special rewards Will be associated with) -Ie" '
:Jhis experiment will be unnecessary if a negative result is obtalnea in Experiment 2.1.
---;A"fti":e-r·t;--he-s~ta-n-.dard training has been completed, i.e., monkeys have achieved a 75% success rate without
special rewards, we will start the physiological recordings from one superior colliculus. The goal will be to char-
acterize the responses oJl" .7/. ;-.___------------.1
( After the Initial recordings are complete, we will concentrate 011 I - raining the animal for about 2-3 months
using the special rewards for either the auditory or visual modalities. The special reward will consist of a large
amount (10-15 times the standard of a leI ra e 'uice' the standard reward is a very small drop of plain water.,
The uestion at this oint will
'-"==-:-:-:::;;::-::-=--;:-:-:-:::::;:-:=:-;.::-=-:=~=:-::-=:;:_:_:==:;::::_=_==_::~=_tt~ a an Glimcher (1999), as well as

many others, have shown that monkeys quickly reco ize..a.cha"ntfg"'e..uID.L.!!."'e~a~dO!.m'..'.i~n,"'is'."tr'.:a'."ti~o~n..':o"..f.'..:re~w:a~r""d:s-"a~n'::'d~q!':u'."IC::':k~ly~
ad'ust their behavior. Accordin I , we anticipate that
e extended training (-2-3

~;;~~~;;;:;~:~~:~~:;::::::::~~~=~~~~~~~_;;~ us, in to-
tal, each of the animals will require an initia peno 0 tralmng 0 a least 6 months, a first (2-3 months) recording
period, a -2 months re-training period, followed by a -2-3 months second recording period. Thus, each experi-
ment will last approximately 1.25 years.
Experimental tasks and stimuli. Both the experimental tasks and stimuli fflr these control experiments will be
identical to those proposed for Experiment 2.1, with .the only difference tha~L_ _ _~_"'IY ________
Data analysIs. I he data ~II

be analyzed as in Experiment 2.1. ]
Potential Problems and Interpretation of Results for Experiments 2.1 and 2.2. The major potential problem
_ _ _ _ _ _ _-...:0{'~_ _ _ _ _ _ _ _ __
with this Aim would be a negative result in Exp 2.1. That isLL-
* G>r(')fr~ ~OCIJ\'n.J.\On
Research Design & Methods )\ Page 40
2011-04-22 000209
Principallnvesligalor/Program Oirector (last, first, middle): POPULIN. lUIS, C
~f this were the case, there will be no need for Exp 2.2; the animals assigned to this experiment, at that
point undergoing the basic part of the training, would be assigned to the experiments of another Aim. Although a
negative result in this case is neither desired nor antici ated, it would still be considered a si nificant contribution
because it would rule out , ¥. . A second
potential problem concerns results of Exp 2.2: it is possible tha _
hat is, expecting a large reward after raining wou ave the same effect on
,.,-------+-:----....1 gain, although this is not the desired or anticipated result we will consider it a
contribution that - erstand the mechanisms of integration in the SC. In both cases ne ative results will
be interpreted a:f-'~=-.::::===:...::..::::...:.:=::.:.::.::.:::~.::::..:::.;{..7-'~=~"""::..:::::::.c."-'-'="--"'="'-'-=~'-"-'=='-!.:."'-l
Specific Aim 3
The representations of auditory space and body surface in the SCi are characterized by their organization
in motor, not sensory coordinates, and by their dynamic modulation by eye position (Groh et aI., 1996; Jay and
Sparks, 1987b; Populin et aI., 2004). The dynamic modulation, which effectively results in shifting RFs as pre-
dicted by the motor error hypothesis (Sparks, 1986), is thought to be a fundamental rnechanism of SC function
to maintain the various maps in spatial register.
This Aim is concerned with a different yet very prominent type of modulation of SCi sensory responses, the
functional significance of which is still unresolved. Specifically. the presence of a second stimulus anywhere in
the field (Populin and Yin, 2004; Rizzolatti et aI., 1974) or the act of fixation (Bell et aI., 2003), results in very
strong suppression of sensory responses. In the cat we have documented a five-fold decrease in the magnitude
of auditory responses in more than 95% of SCi neurons (Populin and Yin, 2002).
Our observations, as well as those of Bell et aI., (2003) and Rizzolatti et aI., (1974) have lead us to hy-
pothesize that the SC functions in two distinct modes: a detection mode, characterized by large responses that
increase the likelihood of detection of events in the surrounding environment and the subsequent orientation to
them, and an attention driven mode, characterized by smaller, transient, but more focused neuronal responses.
--------* ~ specifically hypothesized that • ;--.-~.=~ -\

IS U er 0 eSlze a
Expenmen e hypothesis tested by this experiment concerns exclusively sensory responses in the SCi.
The experiment is best suited for units with circumscribed RFs, although auditory units with large RFs can also
be studied, albeit with more difficulty. The goal will be to ma
-- Experimental desi n and stimuli.

)/c . As demonstrated by
e proximity of the straight ahead position after
in . e. Condition 2 will make use
s emonstrate in Fig 6 of Popu in 2006) in the context of the memory saccade task,
~-------~
-w-·Lhe-n-- -m-o---n-·'k-e-"ys-a=~re-re=q·_--u-ired
to maintain fixation for an extended period of lime thev alinn Ihp.ir heads with (laze
and maintain the position until instructed to orient.{
I -J/----
II he preliminary data (Fig. 7) show tha~
L - _ - - -_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _~_JlhiS strategy
(k~YOpi'~~~orrrn~
2011-04-22 000210
Principallnvesligator/Program Director (Last, first, middle): POPULlN, LUIS, C
has proven productive (Populin, 2005; Populin and Yin, 2002; Populin et aI., 2004) because the selection of the
recording site allow us to anticipate the area of space from which stimuli will have to be presented.
I-'hysiological recordings and analysis. Units suitable for these experiments will be identified during the initial
classification (see above). Visual and acoustic stimuli will be presented from several locations in the context
of the three experimental conditions. Based on our experience mapping RFs ill the SCi of the cat (Populin et
al., 2004), we estimate having to present stimuli from approximately 15-25 locations; this number is perfectly
manageable because our experimental setup is equipped to present stimuli from up to 32 targets. The remain-
ing targets will be presented away from the general area of the RF in order to maintain the animals interested
in participating, and to prevent the neural responses from habituating. The analysis window will be 500 msec
in duration, starting 5 msec after the onset of the stimuli. The average spontaneous rate, computed over a 100
msec window before stimulus presentation in the absence of eye movements, will be subtract from the average
rate computed over the 500 msec window.
For each of the three experimental conditions, the average discharge rate will be computed for each of the
target positions used to map each unit's RF. The area of the RF and its spatial location, the maximal discharge
rate representing the unit's best response area and its spatial location, and the volume of the hill representing
the three-dimensional profile of the RF will be the main variables of interest.
The behavioral responses, i.e., gaze shifts and head movements will be recorded in all experimental condi-
·ons and anal zed as described in Po ulin 2006 ->f:
he alternative result i.e. ,

1---------,;-;-.;o~u:;:ld:;-::n:::o:::ne:::;t"'h:::eT:le::s:::s'b::e:-e~x:::p:::e:::c:;:te:::d:;-;::;to:-:::pr;;:o:;:d;:-:u::::c;:e-;c:;:h::::a::n::ge=s~in~t"h::e:-:m::::agnitude of the responses
evoked from the bes area of a unit's RF; the data from the cat (Populin and Yin, 2002; Populin et aI., 2004; Riz-
zolatti et aI., 1974) and monkey (Bell et aI., 2003) strongly suggest that this will be case. We do not anticipate
failing to document an. effect in light of the existing cat and monkey data.
Either result will have profound consequences for how the SC is thought to perform its sensorimotor integra-
tion functions. Because receptive and movement fields in the SCi are large and broadly tuned (Sparks and Mays, .
1980; Sparks et aI., 1976; Wurtz and Goldberg, 1972), models have resorted to 0 ulation codin schemes such
. Lee et aI., 1988) to generate saccadic eye movements.
Potential problems. I am very optimistic a out positive outcome 0 e

IS experiment based on the strong
modulation observed in the great majority of SCi neurons in the cat (Populin and Yin, 2002; Populin et aI., 2004;
Rizzolalti et aI., 1974) and monkey studies (Bell et aI., 2003). I anticipate, however, encountering a number of
t,." ,... h j)l
I
(~__.p_rn the other hand, will be relatively straight forward because it is clearly defined in most neurons (t:ioraon,
1973; Middlebrooks and Knudsen, 1984). On the positive side,l' >K J
in which to test the hypothesis thatC "'k :
+ 9(O~f~ ~~()Iffi\~
2011-04-22 000211
PrincipallnvestigatorJProgram Director (Last, first, middle): POPULlN, lUIS, C
. k ]
...,.,:-o""--~-,.,.--=-...r) Extensive RF mapping IS time consuming an I Icult to do in a behaving preparation.
Unfortunately, there is no short cut here. Our experience studying RFs in the SC of the cat (Populin et aI., 2004)
leads us to tackle the proposed recordings in the SC of the monkey with great optimism because, (a) this type
of experiment can only be done under conditions of great stability, which our preliminary studies demonstrate
we are able to attain in the HU monkey, (b) the monkey is a much more suitable subject that the cat for this type
RF mapping because it routinel erforms more than 3000 trials per session; the cat performs -300-500. (3)
Stimulus resentation.
I,
he response to this concern IS tree 0 : a we have demonstrated that our mon eys
align e gaze at (or near) the primary position while waiting for the initiation of the next trial (Popu-
lin, 2006), (b) our monkeys exhibit a great d1lgree of discipline in the execution of the experimental tasks; this is
demonstrated by the data shown in Fig 6 of Populin (2006) in the context of the memory-saccade task in which
subjects held both gaze and head aligned with the straight ahead position or hundreds of milliseconds. (c) The
large size of the RFs in the SCi renders small variations in gaze or head position inconsequentiaL
Specific Aim 4
The motor error hypotheSiS (Sparks, 1986) predicts that auditory (and somatosensory; Groh and Sparks,
1996) RFs in the SCi shift with eye position to maintain the auditory and visual representations of space in reg-
ister as the eyes move in the head. The results of tests of the hypothesis in HR animals (Jan and Sparks, 1987;
Populin et aI., 2004) account for only 1/2 to 2/3 of the initial deviation of the eyes from straight-ahead. Two major·
explanations have been offered for the lack of full compensation for eye position: (1) measurement error, in most
cases RFs were sampled on the horizontal dimension and not to their full extent, and (2) gradual transformation
from head to motor error coordinates, with the SC in the middle of process (Jay and Sparks, 1987b).
Undoubtedly, the first explanation is very likely to have contributed to the problem; in addition, Jay and
Sparks (1987b) only analyzed one side of the RFs. Concerning the second explanation, the close association
of the SC and orienting behavior makes it very unlikely that full compensation would be completed elseWhere.
Thus other considerations must be taken into account: (1) In the cat, the magnitude of the shifts of auditory RFs
matches on average the amplitude of eye movements to acoustic targets, which normally undershoot the tar-
gets (Populin et aI., 2004). (2) When the animal is allowed to orient to acoustic targets with the HU, the typical
undershoot of eye movements to acoustic targets disappears (Populin, 2006; Tollin et al., 2005). Thus the HR
condition affects the neural substrate - the auditory RF shift - which defines the amplitude of the resulting eye
movements. Accordin I the h ot 's must be testee{ --t.. .. .
A 1000-1500 msec fixation LED is presented straight-ahead, which the monk uired to fixate until it
is
o eys n pe orm this task without special train-

ing. An a erna Ive ap i=eiatiA§4lle..llliti ion of the eyes and head using a laser mounted on .
*' ]
the subject's head (Gandhi and Sparks, 2.,,0,,0-,,1)'.:r~e~q~ui"-,re::-s..e"'.x,;:te::--n"s...iv~e..t"-,ra~in:"i::n,,"g.~~~~~~~~~_ _ __
. de endent variables will be (1)'
The dependent variables will be (1 ¥
'K (~\Ol?'r~ --Ll\.{orrrn~

2011-04-22 000212
-_._--_. . ..
-- -
%-
- I
uataAnalysis and interpre a Ion or resulls. The Qrimary goals are to determine)
*
The following measures will be used to characterize the auditory RFs:I(l) \
jthe motor error index used by Populin et al. (2004), which takes into account
every data ooi . nf thA RF A mllitinlA linear regression analysis I inA"r MnrlAI will be used. We an-
i )
ticipate (1
*"
those reported by Jay ana ::;parKs, 1 ~tll 0 ana r OpUllil '" al., V:004 J, ana (£ J most importantly, because we will
have both behavioral and physiological data, establish that) X .
.. -. (I
I
/-,otentlal r roV/ems. ,ne tecnmcal complexllY or HIlS expenmenlls aCKnow,eagea. rOnuna,,,'Y, lfIe results ot
our preliminary studies show both their feasibility, and our ability to carry out the pro osed work (Fig. 6,8). The
most difficult challenge will be to obtain ecause extensive
recording times will be required to obtain a a rom a arge num er 0 arge s. ase on our experience in the SC
of the cat (Populin, 2005; Populin and Yin, 2002; Populin et aI., 2004), we estimate that 20-25 targets of the 32
we can control witb olll'-tlardwa ime will suffice; the rest of the available s eakers will be used to re$-'
en We also estimate that give
10-15 trials peLrt""a-:-rg=ce"'ts.,..,..,.w"'illroS:7u,.,,=,cJ!!e;,t-:r-----;r----
.-----~"'~uc-:s:-,71-,<"ftr=;'a;i:Ts:-f<=0-=-r"'25"-'::ta:"::rg-=-e"'tC:-s"(3"'7"'5'"'t"'ri'=-aC::ls')-=-an=-'-d three starting eye positions would require a ota ,of 1125
na s, w Ich constitutes about 1/3 of the average yield of a typical experimental session.
Another potential problem concerns not being able to record from a large enough number o{ ~
- f.. eurons. If this were the case, we will adopt the approach of Gandhi and Sparks (2001 )'-a::::n;;-;a"tr.:ra""ln::-:::-ou:::r::-
~ ith the help of a head-mounted laser. This approach will
. us will allow us to stud~ >K -
·~'---=lIrn1k.o"u",g;>;-''''''',s'""a'''pd.proach will be an alternative, we have started to build the
--=ne~c:::e:-::s:=s""ary::-:-I:-:a:-:r:r.w-;-;a~r:::e..t::-o-::m::o:7u:::n·t-=-aT.la~ser source on the head of the subjects using the head post.
TIMELINE (T =behavioral training; R =physiological recordings; A =data analysis)

I Year 1 I Year 2 I Year 3 I Year 4 Year 5
AIM_1 Exp 1 Monkey A TTTTTRRRAA
Monkey B TTTTTRRRAA
Monkey C TTTTTRRRAAA
AIM 2 Exp2.1 Monkey 0 TTTTRRRAAA
Monkey E TTTTTRRRAAA
Exp2.2 Monkey F TTTTTRRTTRRAA
Monkey G TTTTTRRTTRRAA
AIM 3 Exp 3 Monkey H TTTTTRRRRAAAA
Monkey I TTTTTRRRRAAAA
AIM 4 Exp 4 Monkey J TTTTTTRRRRRAAAA
MonkeyK TTTTTTRRRRRAAAA
Monkey L TTTTTTRRRRRAAAA
2011-04-22 000213
Principal Investigator/Program Director (last, first, middle): POPUlIN,-lUIS, C
F. VERTEBRATE ANIMALS
Species and Justification. The vertebrate animal chosen for the proposed studies is the Rhesus monkey
(Macaca mulatta). The monkeys to be used in the proposed studies will be 12-15 (2-3 monkeys per year)
young males ranging from 5 fa 7 years of age. Three monkeys per year is an adequate number of subjects to
address the proposed questions in light of the extensive training required. This number of subjects is also
appropriate for the size of our experimental facilities and research group. The monkeys will be purchased
from the Wisconsin National Primate Research Center, which is located on the University of Wisconsin-
Madison campus.
The reasons for the selection of the Rhesus monkey for the proposed studies are the following. (1) The
Rhesus monkey is the closest species to man among those available for studies of sensorimotor integration.
Thus, our findings are likely to directly further our understanding of similar neural mechanisms in humans. (2)
The Rhesus mO'nkey is the species of choice for studies of the oculomotor system, a fact that will greatly
facilitate the integration of our results into the published body of knowledge. (3) The Rhesus monkey is an
ideal species for the study of eye-head coordination because under the proper experimental conditions it is
possible to dissociate the movements of the two structures, which is necessary to dissect the contributions of
single superior colliculus neurons to the generation and control of gaze shifts.
Housing and Veterinary Care. All monkeys.will be housed in the Animal Care Facility of the University of
Wisconsin-Madison Medical SchoOl located on .. '*'
!Madison, WI 53706). They will be under the care of the attending veterinary Dr . and herI 't.;;; f
staff of veterinarians and technicians. There is always a Veterinarian on call on the University of Wisconsin-
Madison Campus. . .
All animals are observed on a daily basis by the animal care staff and the PI's laboratory personnel, and
given a physical exam approximately every three months. All surgical and experimental procedures have .
been approved by the University of Wisconsin-Madison Animal Care Committee, and are in strict accordance
with the NIH Guide for the Care and Use of laboratory Animals and the U.S. Public Health Service Policy on
Humane Care and Use of Laboratory Animals.
Surgical Procedures and Training. All animals will undergo at least one sterile surgical procedure to
implant scleral search coils for measuring eye movements, a head coil to me<jsure head movements, a
recording chamber for inserting extracellular recording electrodes into the superior colliculus, and a head
post. Additional surgical procedures, necessary to replace broken eye coils, have been approved by the UW
Animal Care Committee. All surgiclli procedures will be carried out under sterile conditions using gas
anesthesia (isoflurane) in a surgical suit maintained by the Animal Care Facility of the University of Wisconsin
Medical School.
Pain and antibiotics treatments. To ameliorate discomfort during recovery from surgery, we will administer
the analgesics Buprenorphine (0.005-0.01 mg/Kg, 1M), every 6-12 hours, or Carprofen (4 mg/Kg, 1M) once a
day until recovery is complete. Either of these drugs will be administered approximately 20-30 min before the
completion of a surgical procedure.
For antibiotic treatment, we will follow one 9f two options. On the moming prior to surgery the monkey will
be started on a Benzathine Penicillin G and procaine Penicillin G combination (e.g., dual pen, combi-pen,
30,000 IU/Kg, 1M every 72 hours for one to two total doses). Altematively, on the day of the surgery, we will
start injecting Cefazolin (25 mg/Kg, 1M) every 12 hours for 7-10 days. The Veterinarian in charge of the
overseeing health of the animals will make the selection.
After recovery is complete the wound edge around head cap is cleaned before every experimental
session (5-6 times a week) by the laboratory technician or my self. Particular care is to this procedure in order
to avoid the development of infections that could jeopardize the health of the animal and the viability of the
experiment.
Behavioral Training. Before the initial surgical procedure, all monkeys will be trained to enter a primate
Vertebrate Animals Page 45
-'k L()~ ~~ +~\\;~ -t.:)j. J.->. II 0. bOr ~ \.O~~

2011-04-22 000214
Principallnvestigator/Program Director (Last, first, middle): POPULIN. LUIS. C
chair with the collar and pole method using positive reinforcement. After recovery from the initial surgical
procedure, approximately one week, all monkeys will undergo behavioral training on oculomotor tasks (visual,
auditory, and bimodal fixations, standard-, delayed-, and memory-saccades) using operant conditioning.
Water will be offered as a reward after every successful triaL To safeguard against potential dehydration,
each monkey will be carefully weighted every experimental day and the amount of water received in every
experimental session carefully monitored and recorded in laboratory and animal care facility records.
Additional water will be provided after experimental 'sessions as needed in order to ensure that each animal
receives the minimum required by the UW Animal Care Committee: 20 mLlKg. The behavioral training will
last approximately 6-9 months, depending on the skill of the individual monkey. Training will take place 5-6
times per week.
The animals will be continuously monitored while in the experimental room on close circuit TV; a sound
system will also be available to listen to the animals while the are in the experimental room. The primate chair
provides enough space for the monkey to shift his position, but not to turn around. Since the start of our
experimental work with monkeys, we have not found it necessary to interrupt an experimental session
because the animal exhibited signs of discomfort.
Sedation, anesthesia, and euthanasia. In preparation for euthanasia, the monkeys will be tranquilized
with Ketamine (10 mg/Kg), and then deeply anesthetized with sodium pentobarbital (100 mg/Kg, IV). The
veterinary staff is very experienced and competent in this task to minimize the stress, discomfort, and pain
placed on the animals. This method of euthanasia is consistent with the recommendations of the Panel on
Euthanasia of the American Veterinary Association.
While under deep anesthesia the monkeys will be perfused through the heart with saline and formalin
(10%), and the brain recovered for histological processing. Thin sections will be cut through the tectum and
stained with cresyl violet to identify visible electrode tracts.
The Veterinary care of our animals is excellent. A clinical veterinarian is on call 24 hours a day, every day
of the year on the University of Wisconsin Campus. Daily husbandry is under the care of an experience and
dedicated staff. Since the start of our monkey experiments, we have not had any major problems or
compllcatons.
Vertebrate Animals Page 46
2011-04-22 000215
Principallnvestigator/Program Director (last, first, middle): POPULIN, LUIS, C
G. LITERATURE CITED
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Calvert GA, Campbell R, Brammer MJ (2000) Evidence from functional magnetic resonance imaging of
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Driver J, Spence C (1998) Attention and the cross modal construction of space. Trends Cogn Sci 2:254-262.
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Farah MJ, Wong AB, Monheit MA, Morrow LA (1989) Parietal lobe mechanisms of spatial attention:
modalityspecific or supramodal? Neuropsychologia 27:461-470.
Feldon S, Feldon P, Kruger L (1970) Topography of the retinal projection upon the superior colliculus of the
cat. Vision Res 10:135-143.
Finlay BL, Schneps SE, Wilson KG, Schneider GE (1978) Topography of visual and somatosensory
projections to the superior colliculus of the golden hamster. Brain Res 142:223-235.
Fisher NI, Lewis T, Embleton BJJ (1987) Statistical analysis of spherical data. Cambridge UP, Cambridge,
UK.
Freedman EG, Sparks DL (1997a) Eye-head coordination during head-unrestrained gaze shifts in rhesus
monkeys. J Neurophysiol 77:2328-2348.
Freedman EG, Sparks DL (1997b) Activity of cells in the deeper layers of the superior colliculus of the rhesus
monkey: evidence for a gaze displacement command. J NeurophysioI78:1669-1690.
Frens MA, Van Opstal AJ (1998) Visual-auditory interactions modulate saccade-related activity in monkey
superior colliculus. Brain Res Bull 46:211-224.
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2011-04-22 000216
Principallnvestigator/Program Director (Last, first, middle): POPUUN, LUIS, C
Frens MA, Van Opstal AJ, Van der Willigen RF (1995) Spatial and temporal factors determine auditory-visual
interactions in human saccadic eye movements. Percept Psychophys 57:802-816.
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of single neurons. J Neurophysiol 35:542-559.
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neuronal responses. J Neurophysiol 35:560-574.
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activity in primate superior colliculus. J Neurophysiol 75:439-453.
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Populin LC, Yin TCT (2002) Bimodal interactions in the superior colliculus of the behaving cat. J Neurosci
22:2826-2834.
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Sci 956:468-473. .
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stimuli in the superior colliculus of the behaving cat. J Neurophysiol92:2151 -2167.
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movements. In: Progress in oculomotor research (ed Fuchs AF and Becker W) Amsterdam: Elservier/
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of the vestibulo-ocular reflex in these strategies. In: Progress in Oculomotor Research. Fuchs AF, Becker
W (eds) Amsterdam: Elsevier/North-Holland; p. 309-315.
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monkey. J Neurophysiol 34:920-936.
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colliculus ablations. J Neurophysiol 44:1175-1189.
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of primate superior colliculus. Physiol Rev 66:118-171.
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cat superior colliculus. J NeurophysioI39:401-419.
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Principallnvestigator/Program Director (last. first, middle): POPUUN, LUIS, C
Sterling P, Wickelgren BG (1969) Visual receptive fields in the superior colliculus of the cat. J Neurophysiol
32:1-15.
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change during saccade adaptation. J NeurophysioI94:1938-1951.
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disappearance of auditory and visual fixation stimuli. J Cognit Neuroscl 11 :206-213.
Tollin DJ, Populin LC, Moore JM, Ruhland JL, Yin TC (2005) Sound-localization performance in the cat: the
effect of restraining the head. J Neurophysiol 93:1223-1234.
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56: 1542-1557.
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cat. Exp Brain Res 46:448-453. .
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result of impending saccadic eye movements. J Neurophysiol 73:1988-2003.
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J NeurophysioI49:674-685.
Wurtz RH, Goldberg ME (1972) Activity of superior colliculus in behaving monkey. III. Cells discharging
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Yao L, Peck CK (1997) Saccadic eye movements to visual and auditory targets. Exp Brain Res 115:25-34.
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degeneration. Arch Neurol 33:243-251.
References CUed Page 51
2011-04-22 000220
Principallnvestigator/Program Director (Last, first, middle): POPUUN, LUIS, C
PHS 398 Checklist

1. Application Type:
From SF 424 (R&R) Cover Page. The responses provided on the R&R cover page are repeated here for your reference, as you answer
the questions that are specific to the PHS~9B.
* Type of Application:
o New • Resubmission o Renewal o Continuation o Revision

Federalldenlifier: IOC003693 I
2. Change of Investigator I Change of Institution Questions
OChange of principal investigator I program director
Name of former principal investigator I program. director:
Prefix:
I
" First Name: I
Middle Name:
I
"last Name: I
Suffix: I
OChange of Grantee Institution
" Name of former institution:
I I
3. Inventions and Patents (For renewal applications only)
" Inventions and Patents: Yes 0 NaO
If the answer is nYes" then please answer the following:
* Previously Reported: Yes 0 NaO
Checklist Page 52
Tracking Number:
2011-04-22 000221
Principal Investigator/Program Director (last, first, middle): POPUlIN, lUIS, C
OMB Number. 0925·0001

4.• Program Income
Is program income anticipated during the periods for which the grant support is requested?
OYes eNo
If you checked "yes" above (indicating that program income is anticipated), then use the format below to reflect the amount and
source(s). Otherwise, leave this section blank.
'Budget Period 'Anticipated Amount ($) 'Source(s)
c:::J1 II I
ell II I
c:::J1 II I
c:::J I II I
c:::J1 II I
5. Assurances/Certifications (see instructions)

In agreeing to the assurances/certification section 18 on the SF424 (R&R) form, the authorized organizational representative agrees to
comply with the policies, assurances and/or certifications listed in the agency's application guide. when applicable. Descriptions of
individual assurances/certifications are provided at: http://grants.nih.gov/grants/fundingJ424
If unable to certify compliance, where applicable, pr<?vide an explanation and attach below.
Explanation: I I
Checklist Page 53
Tracking Number:
2011-04-22 000222
Attachments
CertificationExpJanation_aHDataGroupO
File Name Mime Type
Checklist Page 54
Tracking Number:
2011-04-22 000223
ESNAP Report FINAL
OMB No. 0925-0001

Grant Number Total Project Period
,
5R01DC3693-6 From: 09/0111999 To: 11/30/2010 )
EIN: Review Group: Requested Budget Period:
SMI From: 12/01/2008 To: 11/30/2009
Title of Project: Due Date: 10/16/2008

Submitted Date: 10/21/2008
Multisensory ~rocesslng in the Behaving Preparation
Program Dlrector/Principallnvestigator: Applicant Organization:
LUIS C POPULIN UNIVERSITY OF WISCONSIN MADISON
UNIV OF WISCONSIN, MADISON UNIVERSITY OF WISCONSIN MADISON
DEPT OF ANATOMY 21 N. Park Street. Suite 6401
1300 UNIVERSITY AVE MADISON. WI 537151218
MADISON, WI 53706
Department: ANATOMY
Phone Number: (608) 265-6451
Fax Number: (608) 262-7306 Major Subdivision: SCHOOL OF MEDICINE AND PUBLIC
Email Address: Ipopulin@wisc.edu HEALTH
Administrative Official: Signing Official:
PhoneNumb~
Fax Number: 6 t
Email Addres ) Phone Numbe?
Fax Number: 6'
Email Addres.
'if
" I
Human Subjects: [Ij No ~ Yes Vertebrate Animals: tel No ~ Yes
Animal Assurance Number: A3368-01
Research Exempt: ® No td Yes
Inventions and Patents: ~ No to Yes
Exemption No: FWA Number: FWA00005399
Previously Reported
Phase III Clinical Trial: ® No td Yes
tel Not Previously Reported
Program Income: ~ No tel Yes
Budget Period Anticipated Amount Source
F&A Changes:
Primary Project/Performance Site Location
Organizational Name: The Board of Regents of the University of Wisconsin System
DUNS: 161202122
I~----------------------------------~--~------------------------------~
Street 1: 1300 University Ave. IStreet 2:
City: Madison ICounty: ISlate: WI
Province: ICounlry: UNITED STATES IZiplPostal Code: 53706
Congressional Districts: 2
PHS2590 Page 1
-'* ::It 'n~1 ~ ~ c.<;,,,+a.ek ~Oltrn~

~~~~
2011-04-22 000224
ESNAP Report FINAL
Program Director/Principal Investigator: Grant Number
LUIS C POPULIN 5R01DC3693-7
Applicant Organization: Period Covered by this Report:
UNIVERSITY OF WISCONSIN MADISON 12/0112008 - 11/30/2009
Tille of Project:
Multisensory Processing in the Behaving Preparation
SNAP Questions:
Has there been a change in the other support of All Personnel since the last reporting period?
I!!J No td Yes
Justification:
Will there be, in the next budget period, a significant change in the level of effort for the PO/PI or other Ait Personnel
designated on the Notice of Award from what was approved for this project?
I!!J No td Yes
Justification:
Is It anticipated that an estimated unobligated balance (including prior year carryover) will be greater than 25% of the
current year's total approved budget?
td No I!!J Yes
Justification: Physiological work in non-human primates is inherently slow. The proposed work will be completed in the
following year. Hence, leftover balanced will be carried forward to the next budget year.
Changes in Select Agent Research? I!!J No [Ij Yes
Changes In Multiple PO/PI Leadership plan? I!!J No td Yes
Change in human embryonic stem cell (hESC) line(s) used? I!!J No td Yes
Justification:
Human Subject Education Requirement:
Has the Involvement of Human Subjects changed since previous submission? I!!J No td Yes
Has the Involvement of Animal Subjects changed since previous submission? I!!J No tC.i Yes
Publications:
Valid NIHMSID: Citation 10: Citation Source: Citation Text:
PHS2590 Page 2
2011-04-22 000225
ESNAP Report FINAL
Research Accomplishments:
File is not uploaded
Other Document File:
Other Support File:
PHS2590 Page 3
2011-04-22 000226
ESNAP Report FINAL
All Personnel Report .
LUIS C POPULIN 5R01DC3693-7
Name: Commons ID: Degree(s) Name: SSN:
lUIS C POPULIN PHD XXX-XX-OOOO Months Devoted
to Project
Role on Project: Supplement Support: DoB: (MMIYY) Cal Acad Sum

PO/PI 1·tfl,{1-
Name: Commons ID: Degree(s) Name: SSN:

C-*---] XXX-XX- Months Devoted
to Project
Role on Project:
Technician
Name:
Supplement Support:
Commons 10: Degree(s) Name:

DoB: (MMIYY)
SSN:
u Acad Sum
1 ;f t XXX-XX- Months Devoted
EJ--
to Project
Role on Project: Supplement Support: DoB: (MMIYY) Sum
Technician
Name: Commons 10: Degree(s) Name: SSN:
L *: I
B
XXX-XX- Months Devoted
to Project
Role on Project: Supplement Support: DoB: (MMIYY) Acad Sum
Technician
Namll,; t "ommons ID: Degree(s) Name: SSN:
1 * XXX-XX- Months Devoted
Role on Project:
Technician
- Supplement Support: DoB: (MMIYY)
EJ to Project
Acad
Sum
Nanm; Commons ID: Degree(s) Name: SSN:
\. ?j£ I XXX-XX- Months Devoted
to Project
Role on Project: Supplement Support: DoB: (MMIYY) Cal Acad Sum
PHS2590 Page 4
2011-04-22 000227
ESNAP Report FINAL
IConsultant
PHS2590 Page 5
2011-04-22 000228
Date: 10/23/2009
TO: NIDCD
From: Luis Populin
Re: Progress Report for project DC003693
The work in this project continues at full speed. We currently have two papers under review
(please see below), and are carrying out physiological recordings from the superior colliculus
of two head-unrestrained non-human primates. We striving to collect data from as many
neurons as possible now that the animals are healthy and in top psychophysical shape.
Concurrently, we are also carrying out the behavioral training of our next two subjects.
Manuscript 1:
Submitted'
Manuscript 2:
Submitted
Luis Populin
2011-04-22 000229
ESNAP Report FINAL
LUIS C POPULIN 5R01 DC3693-6
Applicant Organization: Period Covered by this Report:
UNIVERSITY OF WISCONSIN MADISON 12/14/2007 - 11/30/2008

Title of Project:
Multisensory Processing in the Behaving Preparation

SNAP Questions:
Has there been a change in the other support of Senior/Key Personnel since the last reporting period?
I!!I No lCl Yes
Justification:
Will there be, In the next budget period, a significant change In the level of effort for the PO/PI or other Senior/Key
Personnel designated on the Notice of Award from what was approved for this project?
I!!I No tCi Yes
Justification:
Is it anticipated that an estimated unobligated balance (including prior year carryover) will be greater than 25% of the
current year's total approved budget?
I!!I No tCi Yes
Justification:
Changes in Select Agent Research? I!!I No to Yes
Changes in Multiple PO/PI Leadership plan? I!!I No to Yes

Human Subject Education Requirement:
Has the Involvement of Human Subjects changed since previous submission? I!!I No to Yes
Has the Involvement of Animal Subjects changed since previous submission? I!!I No tr::i Yes
Publications:
Citation 10: Citation Source: Citation Text:

52469 NIHMS Luis C Populin, ; Human sound localization: measurements in untrained,
head-unrestrained subjects using gaze as a pointer; Experimental brain
research. Experimentelie Hirnforschung. Experimentation cerebrale;
PHS2590 Page 2
2011-04-22 000230
ESNAP Report FINAL
Research Accomplishments:
Other Document File:
..
Other Support File:
File Is not uploaded
PHS2590 Page 3
2011-04-22 000231
ESNAP Report FINAL
Senior/Key Personnel Report

LUIS C POPULIN 5R01 DC3693-6
Name: Degree(s) Name: SSN: Role on Project: Months Devoted to Project
LUIS C POPULIN PHD 0000 PD/PI

Cal
[;~ Vum
PHS2590 Page 4
2011-04-22 000232
Progress report for NIH Grant 5RD01DC003693-06.
Since the start of the funding period in we have trained two non-human primate subjects to
perform the behavioral tasks required for physiological recordings from single neurons in the
intermediate/deep layers of the superior collilculus. At this point we are getting ready to begin
such recordings.
The training of these two animals was focused on preparing them to address the hypothesis
outlined in Aim #1 of the grant. In addition, we have recently implanted two additional animals
with eye coils and a head post and began training them. These two animals will be used to
address Aim #2. We anticipate no major difficulties or problems for the work to be completed
in this year of funding.
We have also published a manuscript entitled "Human sound localization: measurements in
untrained head-unrestrained subjects using gaze as a pointer." Exp Brain Res 190: 11-30, and
are finishing a manuscript, to be submitted to the Journal of Neurophysiology, in which we
report the results of a detailed study of the kinematics of gaze shifts to visual, acoustic, and
bimodal (visual + acoustic) targets. We anticipate submitting the manuscript in the first week
of December, 2008.
2011-04-22 000233

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Notice of Award

RESEARCH Issue Date: 03/16/2009

Grant Number: 5R01DC003693-06 REVISED

Project Title: Multisensory Processing in the Behaving Preparation

Award e-malled to: NIH@rsp.wisc.edu

Budget Period: 12/01/2008 - 11/30/2009

Dear Business Official:

Additional information follows

Award Calculation (U.S. Dollars)

Federal Direct Costs $212,500

AMOUNT OF THIS ACTION (FEDERAL SHARE) $31,237

SUMMARY TOTALS FOR ALL YEARS

IC CAN 2009 2010

NIH Administrative Data:

SECTION 11- PAYMENT/HOTLINE INFORMATION - 5R01DC003693·06 REVISED

SECTION /11- TERMS AND CONDITIONS - 5R01DC003693·06 REVISED

(See NIH Home Page at 'http://grants.nih.gov/grants/policy/awardconditions.htm' for certain

This grant is subject to Streamlined Noncompeting Award Procedures (SNAP).

Treatment of Program Income:

SECTION IV - DC Special Terms and Conditions - 5R01 DC003693·06 REVISED

Grants Management Specialist: Hoai Doan

Program Official: Christopher Platt

INSTITUTION: UNIVERSITY OF WISCONSIN MADISON

Facilities and Administrative Year 6 Year 7

To Whom It May Concern:

. the following grant application submitted to NIH

Most Recent Committee Re-review: 02111/2009.

Name of Principal Investigator: Populln, Luis C.

Address: Medical Sciences Ctr., 1300 University Ave., 8385

Title of Grant Application: Multisensory processing In the behaving

Name of Animal Care and Use Committee: SMPH

Name of Chairperson: Dr. Amy Moser

Research Animal Resources Center

Received: 03/05/2007 FOA: PA07-070 Council: 10/2007

Competition 10: FOA Title: RESEARCH PROJECT GRANT (PARENT R01)

2 R01 DCOO3693-0SA1 Dual: NS Accession Number: 2978361

IPF: 578503 Organization: UNIVERSITY OF WISCONSIN MADISON

Former Number: Department: ANATOMY-GEN

IRG/SRG: SMI AIDS:N Expedited: N

Subtotal Direct Costs Animals: Y New Investigator: N

SeniorlKey Personnel: Organization: Role Category:

LUIS POPULIN The Board of Regents of the University PO/PI

SF 424 (R&R) 02/14/2007

5. APPLICANT INFORMATION .. Organizational DUNS:161202122

Person to be contacted on matters involving this application

Reeefved Dale: Time Zone: GMT·S OMe Number: 4040.0001

0 PROGRAM HAS NOT BEEN SELECTED BY STATE FOR REVIEW

19. Authorized Representative

, Signature AuthO:d R.e[~··rtlve. • Date Signed

20. Pre..appllcatlon File Name: Mime Type:

424 R&R and PHS·39B Specific

Research & Related Other Project Informatlon··································-····· .. •• ....................................... . 5

Project Summary/Abstract (Description)·····-············ ...... ················~··....................... . 6

Public Health Relevance Statement (Narrative attachment) .. ······u.............................. 7

Facilities & Other Resources.····· ..•••·••·•·• ..··············~· ..·· .. ······•................... . 8

Eq uip ment································ .. ·•·•··•· .. ··•..•··• .•.••..••.....

Biographical Sketches for each listed Senior/Key Person···················_········ .. ·..•· .. •••·••·•· .. • 12

PHS 398 Specific Cover Page Supplement··········· oaoa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

PHS 398 Specific Modular Budget····················· .. ·••·•··•····••········•··· ..................................................... . 16

Personnel Justification········································· •.....•.••.•....•....•.•.• 20

PHS 398 Specific Research Pian·················································· ..............................._ .................... . 21

Introduction to Revised/Supplemental Application·····················.... ··••··••·••·•• .. •··•• .......... . 24

Significance and Related R&D···~····· .. ··•··•·•••••··•··•·••··•·••·•·•.. ···---···••.•••••.••• 28