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Learning and Memory

Define two phases of memory: short term, long term. What are the
general differences?
Short term memory is labile, meaning it can be formed very quickly, but also lost
quickly
cells dont need to make new parts (protein synthesis independent)
declarative memories are easily formed and easily forgotten
result from small modifications of synapses
Long term memory is stable because it can last days, weeks, a lifetime
changes in the structure of neurons allows for formation of long term memories
(protein synthesis dependent)
involves structural changes
procedural memories involve learning a motor response in reaction to a sensory
input
non-associative and associative learning
Define. Give an example of each.
non-associative learning
change in behavioral response to a single stimulus over time
two types: habituation and sensitization
habituation
learning to ignore a stimulus that lacks meaning
the same stimulus produces a progressively smaller/weaker response
ex. putting on socks, initially you can feel them, but after a while on, you dont
sensitization
heightens perception and ability to respond in response to stimulus
ex. during a blackout you hear footsteps and startles you, normally this would not
cause such a reaction in daylight, but the strong sensory stimulus (blackout) caused
sensitization
Explain gill withdrawal reflex in Aplysia: siphon, gill, gill muscle. Draw
simple homo-synaptic and hetero-synaptic circuits.
Aplasia = marine snail with large, simple neurons
Gill withdrawal reflex: repeating poking causes habituation and decreased
withdrawal response
Habituation occurs with decrease in size of postsynaptic EPSP

Siphon: touch to siphon (a sensitizing stimulus) causes signal in motor neuron to

Habituation (L)
Sensitization (R)

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withdraw gill
Habituation: how do presynaptic and postsynaptic responses change?
Habituation occurs with repetitive stimulation to sensory neuron, causing decrease
in size of postsynaptic EPSP
After habituation, there are fewer NT molecules released per AP
Sensitivity of postsynaptic cell to NT does not change, so habituation of gillwithdrawal reflex is associated with presynaptic modification
Sensitization: Explain behavioral test. Draw simple circuit, explain
synapse of facilitatory neuron onto sensory neuron axon terminal.
To cause sensitization, electric shock applied to head of Aplysia
Caused exaggerated gill withdrawal in response to stimulation of siphon
Modification in NT release in the sensory nerve terminal
L29, a third cell, is activated by the head shock and makes a synapse on the axon
terminal of the sensory neuron
L29 releases serotonin, sensitizing sensory axon terminal (G-protein coupled
metabotropic receptor) so that it releases more Ca per AP
Stimulation of this receptor leads to release of second messenger, cAMP, then
protein kinase A, which phosphorylates K channel to close, causing prolongation of
presynaptic AP (more Ca, and more NT)
Summary: L29 releases serotonin, increasing protein kinase A, closing K channels,
increasing Ca and NT release

List molecular steps in sensitization response: serotonin, serotonin

receptor, cAMP, PKA, K channels.
L29 synapses onto sensory axon terminal, releases serotonin onto the G-coupled
protein receptor, which releases cAMP, increasing released of protein kinase A,
which phosphorylates K channels (closes them), causing prolongation of presynaptic
AP and increases Ca and NT release
Explain effect of phosphorylated K channels on: the duration of the
presynaptic action potential, voltage-gated Ca2+ channels, Vm,
neurotransmitter release. How does this cause an exaggerated response
to touch to the siphon?
Release of protein kinase A phosphorylated K channels, which causes it to close
Closure of K channels leads to prolongation of presynaptic AP (Vm is longer)
Results in more Ca entry through voltage-gated calcium channels during AP, and
more NT release and an exaggerated response to touch on the siphon
Draw a performance curve for a normal animal, a learning mutant, and a
memory mutant.
Amnesia inability to form long-term memories
The higher the performance index the better
wild-types gradually decrease performance index
In amnesiac memory mutants, after training their memory is quickly lost
learning mutants have a really low slope because they do not learn as fast

State the two parts of Hebbs postulate.

Correlated firing patterns cause stronger synapses
Neurons that fire together, wire together.
Uncorrelated firing patterns cause weaker synapses
Out of synch, lose the link.

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Define LTP; describe the experimental strategy to induce LTP.

Long-lasting enhancement in the strength of stimulated synapses in the
hippocampus
Discovered by Bliss and Lomo
Induced LTP through high frequency stimulation to the same axons
Hippocampal LTP is input specific
High frequency stimulation is not a requirement for LTP, rather synapses must be
active at the same time that the postsynaptic CA1 neuron is strongly depolarized
Hetero-synaptic and associative
Activity in one synapse can affect post-synaptic responses in another synapse
IF both synapses are active at around the same time
What are the two glutamate receptor types that are involved in LTP?
Compare and contrast. What is the function of each in LTP?
AMPA: Glutamate opens; passes Na and causes EPSP in postsynaptic neuron
most important receptors for actual excitation
NMDA: glutamate will bind to them but wont open because Mg blocks if at resting
Vm
Needs both pre- and post-synaptic activation
NMDA receptors change the strength of the synapse
Done by adding more AMPA receptors
Conduct Ca, but only when glutamate binds and postsynaptic membrane is
depolarized enough to displace Mg ions that clog the channel
Ca entry through NMDA receptor signals pre/postsynaptic elements active at same
time
LTP induction is prevented if NMDA receptors are pharmacologically inhibited or if
rises in postsynaptic Ca are prevented by injection
Describe the role of each in LTP: NMDA receptors; Ca++; movement of
AMPA receptors; dendritic spine growth.
LTP: synapses get stronger by growing larger dendritic spines
New synapses formed by new spines
Larger spines create a stronger synapse
Can contain more AMPA receptors, so more responsive to glutamate
LTP: synapses get stronger by adding AMPA receptors
Eye development and evolution:
What is the developmental evidence that the eye is a CNS structure?
Inductions of lens by optic vesicle
Eye is an outgrowth of the forebrain (diencephalon)
Starts off as a bulge of the diencephalon, then forms eye cup, connected to brain
through optic nerve
Describe early stages of eye morphogenesis: what embryo tissue does
each derive from? Neural plate, Eye field, optic groove (or pit), optic
vesicle, optic cup?
Lens forms from surface (skin) ectoderm
retina comes diencephalon
Surface ectoderm becomes cornea
Optic vesicle: outgrowth of forebrain
Neural retina

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Epithelium proliferates, forms optic cup

Progenitor cells differentiate into neurons
Several neuron types for retinal network
Neural Crest (cells migrate out of neural tube)
Iris muscles; pigments (blue, brown, green, etc.)
Define:
eye field:
the part of the embryo that could become eye
eye field transcription factor:
Several transcription factors (Pax6, Rx, Six3, Optx2, etc.) expressed in neural plate
eye field transcription factors (EFTF) activate each other
cyclopia:
single fused eye, missing midline structures, lethal
Caused by lack of midline tissue, or disruption of SHH signaling (cyclopamine)
holoprosencephaly:
Caused by lack of midline tissue, or disruption of SHH signaling (cyclopamine)
failure of telencephalon (forebrain) to split into two cerebral hemispheres
Explain how disruptions of the midline signal, Sonic hedgehog, can cause
cyclopia.
Sonic hedgehog is a signaling protein
mutations in sonic hedgehog causes fusion of two brain hemispheres
SHH secreted to split to define two eyes
initially a broad region of anterior embryo
Explain Spemanns lens induction experiment.
Skin did not organize on lens, showing optic vesicle signal lens formation
cut off the optic vesicle during early development, lens did not form
concluded there must be a signal going from optic vesicle for lens formation
For each of these examples, explain how this shows the importance of
Pax6 transcription factor:
Evolutionary conserved gene sequence:
Pax6 gene expression in the embryo:
Expressed in early eye and brain structures
Pax6 gene is a master regulatory gene for eye development
Phenotype of Pax6 mutations:
Drosophila: Eyeless mutation; failure of eye development
Can also be forced expressed in other tissues, causing eyes on ectopic places like
the leg or antennae
Mouse Pax6 mutation:
Heterozygotes have small eyes
Homozygous mutants have optic vesicles, but do not develop retina or lens
Human: aniridia:
heterozygotes: lack of iris (colored part of eye); just one giant pupil
homozygote: one known case; no eyes, died at one week of age with severe brain
and craniofacial defects
What results from mis- expression of Pax6 in developing fly legs? What
experiment shows that the human Pax6 gene has the same activity as the
fly Pax6 gene?

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Ectopic expression of Pax6 gene in leg results in leg developing into a compound
eye
Same results occur if human or mouse Pax6 gene is used to mis-express gene;
creates a fly eye, not human or mouse eye
Define:
progenitor cell:
like a stem cell, has a tendency to differentiate into a specific type of cell, but is
already more specific than a stem cell and is pushed to differentiate into its
"target" cell
pass through competence states
lateral inhibition:
suppresses neuron program in most cells
disables the spreading of APs from excited neurons to neighboring neurons
can control proper number of neurons from differentiating
What is the role of each in lateral inhibition: (Draw the feedback loop
between these proteins?)
Delta:
Ligand for Notch receptor
Feedback loop leads to lateral inhibition
Delta binds to and activates Notch
Contact signaling, not secreting
Notch signaling represses Neurogenin
Neurogenin normally activates Delta, and promotes neuron differentiation program
Notch:
Once Delta binds to and activates Notch, Notch signals to repress Neurogenin
Neurogenin:
Expressed in endocrine progenitor cells; transcription factors involved in specifying
neuronal differentiation; normally activates Delta
Since Notch represses Neurogenin, Neurogenin does not get to activate Delta,
decreasing Delta
Summary: Delta binds to and activates Notch, Notch signals to repress Neurogenin,
Neurogenin does not get to activate Delta

Negative feedback loop

Predict the effect of reducing Notch signaling in a progenitor cell? What is
the effect on neighboring cells of reducing Delta?

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Reducing Notch would increase activation of Delta through Neurogenin, which

increases differentiation of progenitor cells
Ex. Reducing Notch signaling increases NeuroD, resulting in more neurons
Reducing Delta through Notch signaling decrease differentiation of neighboring cells
Notch signaling = less Delta and Neurogenin aka less cell differentiation
No Notch signaling = increased cell differentiation
What type of proteins are the pro-neural genes? How do embryo cells
respond to expanding expression of a pro-neural gene?
NeuroD: involved in the differentiation of nervous system
Gain of function of NeuroD in embryo cells creates the expansion of the nervous
system
More neurons
Conversion of epidermis to neurons
Topographic mapping: define:
retino-tectal map: frogs eyes send axons to tectum

Dorsal V
Ventral D
Nasal P
Temporal - A
tectum:
retinal axon connections make map in tectum
responsible for auditory and visual reflexes.
What is the main target of retinal axons in: frog, human?
In frogs:
Left eye retinal axons go to right tectum and vice versa
In humans:
Left eye retinal axons go to both left and right thalamus (LGN)
Do retinal axons fully cross at the optic chiasm in frog? In human?
In frogs:
Retinal axons project to the opposite side of the brain
Complete crossing
In humans:
Axons from one eye have split projections
Part of visual field is projected across, part is sent to same side

Draw and label quadrants of the retina and tectum: dorsal-ventral, nasaltemporal, anterior-posterior.

Draw the projections from each sector of the retina to each sector of the
tectum.
D- V T-A
V-D
N-P
Define:
functional molding hypothesis:
connections are set up randomly and adapt themselves through experience
(learning)
chemoaffinity hypothesis:
axons discriminate between different areas of tectum and match up with
appropriate targets
ability to detect chemical cues in the tectum (lock and key specifity)
Describe Roger Sperrys frog eye rotation experiment. What was the goal
of the experiment?
He cut and rotated the optic nerve of a frog
The optic axons regenerated their connections to the tectum after a few months
The frog never learned to compensate for the rotated eye, so would strike the
opposite direction of the fly
argues against functional molding hypothesis since the axons returned to their
original targets in the tectum

Describe the result of the frog eye rotation experiment: behavioral, and
anatomical.
Axons returned to their original targets in the tectum
Frog never learns to adapt; would strike in the opposite direction of the fly
For axons within the rotated retina, list and draw where they target in the
tectum: Dorsal, ventral, temporal, nasal.
Dorsal V
Ventral D

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Temporal A
Nasal P
Same as before, just eye is rotated 180 counterclockwise

Explain whether this provides support for functional molding or

chemoaffinity?
argues against functional molding hypothesis since the axons returned to their
original targets in the tectum (chemoaffinity)
chemical cues guide axons to their correct target
Describe the stripe assay for testing retinal axon outgrowth.
Retinal axons prefer to grow on cell membranes isolated from their tectal target
In the assay, cell membranes painted in stripes
Axons grew on a piece of retina
Temporal axons were repelled from posterior tectal membrane and attracted to
anterior (T-A)
Nasal axons were not affected by repellent
Do temporal retinal axons prefer to grow on posterior or anterior tectal
membranes?
anterior
Describe the expression pattern of ephrinA ligands in the tectum, and
EphA receptors in the retina.
Eph ligands repels axons
Ephrin ligands are expressed in gradient in tectum
Eph receptors are expressed by retinal axons
High temporal, low nasal

Eye evolution:

Why was this an important puzzle for Darwin to explain?

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Eyes are complex so they could not have evolved in one step since structure needs
specific organization for vision to work
How many times have eyes evolved during animal evolution?
At least about 100 times
Compare and contrast the camera eyes of squid and vertebrate (one
similarity, one difference).
Similarity:
Evolved from animal photoreceptor cell precursor (PaxB, c-opsin)
Difference:
Squid camera eye is rhabdomeric photoreceptor
o do not have a blind spot
Vertebrate camera eye is ciliary photoreceptor
Octopus camera eye has inverted retina and developed from pocket of skin vs. an
outgrowth of the brain as in humans
List three possible intermediate stages of eye evolution.
Flounder fish
patch of photoreceptor cells on the skin of an animal
List the common cellular and molecular elements of every type of eye:
Photoreceptor: photoreceptive proteins
eye field transcription factors:
opsin: opsins
Axon guidance:
Define:
growth cone: the growing tip of the axon
actively seeks cues
senses and responds to environment
navigates long distances through the developing brain and body
guidance cue:
signaling proteins that steer axons
attractant: an agent that attracts or lures
repellent: an agent that repels or wards off
What are the functions of each in the growth cone?
Microtubules:
move vesicles, granules, organelles like mitochondria, and chromosomes via special
attachment proteins (transportation)
linear polymers of tubulin that serve a cytoskeletal role
new molecules get added on to the ends of the tubules
actin-myosin:
responsible for cell movement
also, crawling movements of cells across a surface
myosin is a motor protein that helps with force and movement
membrane vesicles:
form naturally during the processes of secretion (exocytosis), uptake (endocytosis) and
transport of materials within the cytoplasm
filopodia
retract and extend
Involved in steering the growth cone

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List the four main families of guidance cues. Guidance cues are what type
of proteins?
Netrin
secreted proteins
Sema3
Slit
secreted proteins
Ephrin
cell surface proteins
Guidance cues or diffusible molecules
cell surface secreting proteins
Netrin is a chemoattractant that attracts the axons of dorsal horn neurons through a
gradient
What makes a guidance cue attractive or repulsive? (depends on the
receptor type)
Depends on the receptor expressed by the axons
Chemoattractant is a diffusible molecule that acts over a distance to attract growing
axons toward their targets
Ephrins are one repulsive signal for temporal retinal axons
Secreted in a gradient across the surface of the tectum, with the most on posterior
tectal cells
Gradients in the expression of guidance cues and their axonal receptors can impose
considerable topographic order on the wiring of the retina to its targets in the brain
Commissural axon guidance: describe the location of their cell bodies,
and the trajectories of their axons.
Axons grow toward and across midline
Links sides of brain
Floor plate is key source of cues
Axons grow along length of neural tube
floor plate continuously produces netrin and slit chemicals to attract axons to
midline
slit repellent receptors activated after crossing,
Explain the sequence of events that guide commissural axons across the
floor plate: what are the active receptors on the growth cone before,
during, and after crossing.
Attracted by floor plate
Grow ventrally to floor plate
Cross midline
Turn to grow longitudinally on contralateral side
Adhesion promotes crossing
Axons switch responses: repellent pushes axons away
active receptors on the growth cone before crossing: Netrin attractant receptors
(DCC)
during: did not say
after: Robo receptors (repellent)
Netrin receptors are still active (as shown in Dr. Masticks lab)
Which are the main guidance cues that guide commissural axons?

Secreted attractants: Netrin and Sonic Hedgehog

Secreted repellents: slits (ventral) and BMPs (dorsal)
Describe evidence that the floor plate is attractive, and that Netrin is the
attractant. (Netrin1 mutant mouse embryos).
Netrin is an attractant, slits are the main repellents
Silencing of attraction
Post-crossing axons do not turn in response to netrin like in the floor plate
Netrin mutants shift away from midline of floorplate and express growth defects
Truncated bundles are seen because axons leave and rejoin
Longitudinal guidance: define longitudinal axon trajectory.
Longitudinal axons are guided by Slit/Robo signals from the floor plate
have both sets of receptors active (attractant and repellent)
in a balance to grow longitudinally

Describe the evidence for the push-pull model, with Netrin attraction and
Slit repulsion.
Slit repellents keep longitudinal axons out of floor plate (push away from midline)
Netrin attractants pull axon towards floorplate
Axons can respond to both slit and netrin cues at the same time
Contradicts silencing model
Comprehensive section of exam.
Final exam study guide: This list of things to know for the final exam covers
the most important material in our course, but it is still a lot of material. This list is
about half of the material listed in the study guides for each individual exam. The
information on the learning and development lectures is more detailed.

Cell biology of neurons and glia.

Define and explain the Neuron doctrine. (by Ramon y Cajal)
Neurons are the fundamental unit of the nervous system
Neurons are discrete and separate
Not merged together
Neurons have three parts
Cell body, axons, dendrites
Axons and dendrites represent greatest membrane surface area in neurons
Signals flow in one direction
From dendrite to axon

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Explain the contributions of Cajal and the Golgi stain method.

Golgi soaked brain tissue in silver chromate solution in which soma and neurites
could be seen
Cajal took this method and came up with the neuron doctrine
Stated neurons are discrete and separate (opposite of was Golgi proposed)
Communicate by contact, not continuity
Define and briefly explain function of basic cell structures:
Soma
Cell body
Contains cytosol and organelles (same as those found in all animal cells)
Cytoplasm
Everything found inside the cell membrane excluding the nucleus
Organelles
Nucleus, rough ER, smooth ER, Golgi apparatus, and mitochondria
rough endoplasmic reticulum
contains ribosomes
major site of protein synthesis
RNA transcripts bind to ribosomes, which translate RNA to protein
smooth ER
does not contain ribosomes
site for preparing proteins for delivery to different cell regions
believed to be a site where proteins are folded into their 3-dimensional structure
regulate internal concentrations of substances (like calcium)
Golgi apparatus
Stack of membrane-enclosed disks farthest from nuclei
Site of protein sorting for delivery to different cell regions
Mitochondria
Site of cellular respiration
Inhales to pull in pyruvic acid and oxygen floating in the cytosol, enters Krebs
cycle to produce ATP
phospholipid bilayer
polar membrane made of two layers of lipid molecules
polar, hydrophilic head; nonpolar, hydrophobic tail
cytoskeleton
internal scaffolding for neuronal membrane
dynamic; made up of microtubules, microfilaments, neurofilaments
microfilaments
braids of 2 strands, which are polymers of actin protein
closely associated with the membrane
play a role in changing cell shape
Microtubules
Big and run longitudinally down neurites; railroad tracks
Hollow core
Consists of tubulin
Minus-end closest to cell body, positive-end towards axon terminal
No microtubules in axon terminal
intermediate filaments
diverse proteins that polymerize
many are specific to neuronal types

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exists in the body as intermediate filaments, and neurofilaments in neurons

neurofilaments are very strong
ex. Keratin; when bundles, makes hair
Actin
actin polymers make up microfilaments
force producing
concentrated in growth cones, where growth is active
Tubulin
Thick polymer tubes; stiff
How are microtubules polarized in neurons?
Polymerization, the process of joining small proteins to form a long strand, results in
a polymer
Microtubule-associated proteins (MAPs) anchor microtubules to one another and to
other parts of the neuron
Explain the mechanisms of axoplasmic transport: anterograde motor,
retrograde motor, Plus end, minus end.
No ER in axon, so no protein synthesis occurs here; proteins derived from soma
Axoplasmic transport: movement of material down the axon
Material in the vesicles walk down the microtubule with the help of kinesin protein
and ATP
Anterograde motor: movement of material from soma to terminal
Moves toward positive end of tubule
Kinesin: plus-end directed motor
Retrograde transport: movement of material from terminal to soma
Though to signal to the soma about metabolic needs of axon terminal
Moves toward negative end of tubule
Dyein: minus-end directed motor
Name the four types of glia, briefly explain their function. For each, are
they in PNS or CNS?
Astrocytes
Fills in space between neurons
Oligodendrocytes
Myelination
Schwann cells
myelination
microglia
act as phagocytes of the brain
Explain myelin formation and its function in propagating action potentials.
The Action potential.
Basic definitions: resting potential, action potential, charge, voltage,
current, resistance, conductance, permeability.
Equilibrium potential = voltage
Define and explain properties of the action potential: threshold, frequency,
amplitude, refractory period, subthreshold response.
Explain electrochemical gradients and the reaction of ions to these gradients.

Explain the parts of the Nernst equation: a simple version is Ex=(60/z) log
([X]out/ [X]in)
Ex = electrical gradient
Log(ion) = chemical gradient
Z = charge (+/-)
Explain equilibrium potential: the electrical gradient that will counteract
the chemical gradient.
Know log base 10 of 100, 10, 1, 0.1, 0.01. (hint: count decimal places)
Log10 = 1; log 100 = 2; log1 = 0; log0.1 = 1; log0.01 = 2
Be able to estimate whether the Ex for an ion is + or based on the
concentration gradient and charge on the ion.
K greater on the inside negative charge
Na greater on the outside positive charge
Ca greater on the outside positive charge
Cl greater on the outside negative charge
Memorize the approximate Ex for typical gradients of Na+, K+, Cl-, Ca++.
K = -80mV
Na = 62mV
Ca = 123mV
Cl = -65mV
Be able to calculate using Nernst equation the Ex for a given ion gradient.
Describe the role of the Na+/K+ pump, long term and short term, hours
and msec.
Does not play a role in the action potential
Enzyme - breaks down ATP when Na present
3 Na in, 2 K out
Define and label a graph of an action potential: depolarization,
repolarization, hyperpolarization, resting membrane potential. Mark the
ENA and the EK.
ENa = +60mV
EK = -80mV
Describe how PK and PNa compare during each phase of the action potential.
Given a graph of an altered action potential, predict which type of channel
is being blocked:
TTX: Na channel blocked, no AP
TEA: K channel blocked, leak K not allowed, K builds up and AP occurs
w/o stimulus
Two examples: 1) lower amplitude, but normal repolarization. 2) Normal amplitude,
but slower repolarization.
Describe the three states of a voltage-gated Na+ channel. How does each
state contribute to the phases of the action potential?
Closed, ready
- Resting membrane potential

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- depolarized
Closed, inactivated
- Refractory period
How do these conditions increase rate of conduction: more channels,
increased density of channels, larger diameter axon, myelin?
Larger axons = faster rate of conduction
More channels =
Increased density of channels = faster depolarization?
Myelin = faster rate of conduction
Synaptic transmission.
Define: Presynaptic, postsynaptic, axon terminal, active zone, synaptic vesicle,
synaptic cleft
What are the key features of the neuromuscular junction? Size, neurotransmitter,
excitatory or inhibitory, type of receptor.
List the sequence of events in synaptic transmission.
List the steps in neurotransmitter release. Which need to occur before the arrival of
the action potential?
Name and describe the function of three proteins associated with the membrane of
synaptic vesicles.
Describe the functions of SNARE complex proteins in synaptic vesicles.
Define neurotransmitter receptor types: ionotropic, metabotropic. Which is faster?
Define: epsp, ipsp. Draw a graph for each.
Which ionotropic receptors would be excitatory or inhibitory? Na, K, Cl, Ca
Explain how the ACh receptor is excitatory? What is its ion specificity?
Explain how neurotransmitter signaling is terminated: diffusion, reuptake,
degredation.
Define: agonist, antagonist.
Neurotransmitter systems.
Explain the ACh cycle: ACh transporter, AChE, Choline transporter, ChAT.
Briefly explain the molecular cause of Parkinsons disease.
Explain the mechanisms of actions of these drugs: MAOIs, SSRIs, LSD,
amphetamines
State the major functions of glutamate, GABA in the human CNS.
Compare and contrast the AMPA and NMDA glutamate receptors.
Chemical Senses:
Taste: what types of chemicals can be sensed? List 5 taste qualities of tastants.
Smell: what types of chemicals can be sensed? How many olfactants?
Explain: many tastes that we perceive are actually smells.
Taste:
Define and list properties of: taste bud, taste receptor cell.

For each of the five types of tastants, describe how taste is transduced, how
receptors function.
Describe olfactory neuron regeneration cycle, role of basal cell.
Glomerulus: explain location, structure, function. Which inputs does a single
glomerulus receive?
Olfactory receptor proteins: explain protein structure, signaling mechanism
(contrast with phototransduction).
Olfactory receptor gene family: number of genes, organization in genome,
properties of human gene family.
How many olfactory receptor types are expressed by a single olfactory neuron?
How many receptor types does a specific olfactant bind to? How many different
olfactants can a specific receptor bind?
Vision: retina.
Describe the density of cones and rods across the retina.
List the five main neuron types in the retina, and draw the synapses that each cell
type has.
What is the response of photoreceptors to light: On or off? Describe the
electrophysiology in terms of ion channels.
Outline the phototransduction signal cascade. Name each major component;
describe which steps result in amplification. (Opsin, two forms of retinal,
transducin, phosphodiesterase, cGMP, cation channels)
Describe the receptive field of off-type bipolar cells, on-type bipolar cells.
Describe and draw the synaptic inputs, outputs, increase/decrease in membrane
potential, and neurotransmitters produced by: photoreceptors, off-type bipolar
cells, on-type bipolar cells, horizontal cells.
Why is glutamate excitatory for off-type bipolar cells but inhibitory to on-type
bipolar cells?
Explain the lack of response of bipolar cells to diffuse light in their receptive fields.
Color vision: what sets the responses of cones to different wavelengths of light?
Explain how comparison of signals from different cone types is required for color
vision.
Describe the molecular genetic causes for red-green color blindness.
Vision: brain.
Describe and draw the visual projections from retina to LGN to primary visual
(striate) cortex.
Define topographic map; retinotopic map; retinofugal.
Define optic chiasm.
Axons from which region of the retina cross at the chiasm? Which do not cross?
Define: ocular dominance, ocular dominance columns, layer IV.
Critical period and plasticity: describe and explain how the critical period for ocular
dominance columns can be defined (monocular deprivation in kittens).

1.
a.
2.

Draw the LGN projection patterns from each eye to primary visual cortex, in these
conditions:
young kitten (before eye opening),
normal kitten just after eye opening,
normal adult,
adult after 1 week of monocular deprivation during critical period,
adult after developing with normal open eyes but then treated with 6 months of
monocular deprivation during adulthood.
Draw and explain the receptive field of a simple cell in primary visual cortex.
What pattern of ganglion cells results in the simple cell receptive field?
Auditory system:
Explain how sound waves physically vary in pitch and intensity.
Draw a basilar membrane with frequency map. Explain what the frequency map
means.
Explain mechanotransduction mechanisms in stereocila.
Define tonotopic map.
Explain the two mechanisms of frequency coding, in terms of auditory nerve activity
patterns (phase locking, tonotopy).
Sound localization mechanisms: interaural time delay; interaural intensity
difference.
Duplex theory of sound
sudden or low frequency sounds (long waves)
our auditory system can pick up time delays from one peak to the next
high frequency and continuous sounds
interaural time delay: sudden or low frequency sounds
Interaural intensity difference: high frequency or continuous sounds
less precise
Define duplex theory of sound localization. Which mechanism would be useful to
localize: sudden sound, low frequency continuous sound, high frequency
continuous sound.
Explain mechanism of detecting interaural time delay: superior olive inputs,
preferred delay time, delay lines.
Motor lectures:
Define:
flexor:
movement in the direction that closes
ex. biceps
extensor
movement in the direction that open
ex. triceps
concentric
force that occurs when muscles shorten
isotonic
eccentric

 force that occurs when muscles lengthen

isotonic
ipsilateral
same side
contralateral

opposite side
Define the two types of lower motor neurons: explain function of each.
Alpha motor neuron

Directly triggers generation of force by muscles

Gamma motor neuron
Innervates intrafusal muscle fiber of muscle spindle
Lower motor neurons are the only to directly command muscle contraction
Define:
motor unit:
one motor neuron plus the muscle fiber(s) it controls
motor pool:
collection of motor neurons that innervate one muscle
Draw a map of how limb motor neurons are topologically organized in the

ventral horn.
What are the three major inputs to motor neurons?
Spinal interneurons
Muscle spindles
Upper motor neurons in the brain
Define graded muscle contractions; explain temporal summation, tetanic
stimulation.
Graded muscle contractions:
Temporal summation in motor unit
Temporal summation:

 Occurs when a single presynaptic neuron fires many times in

succession, causing postsynaptic neuron to reach its threshold and fire and
AP
Tetanic stimulation:
Max plateau of contraction
Graded contractions: what size of motor units are recruited first?
Smallest first, then larger one are recruited for a stronger contraction
Define role for each:
Muscle spindle: also called intrafusal muscle
Consists of several types of specialized skeletal muscle fibers
contained in a fibrous capsule

Intrafusal muscle:
modified skeletal muscle fibers within muscle spindle capsule
receive motor innervation by gamma motor neurons
extrafusal fibers receive innervation from alpha motor neurons

proprioreceptive sensory axon

specialized for the detection of changes in muscle length

gamma motor neuron

innervates intrafusal muscle fibers at the 2 ends of the muscle spindle
activation of fibers causes a contraction of the 2 poles of the muscle
spindle, pulling non-contractile equatorial region and keeping 1a axons active
Myotatic reflex (for example, patellar reflex): know overall function, list
all cells (sensory, interneuron, motor), draw locations, know excitatory or
inhibitory function of each synapse.

Function: restore length

Know the same for: inverse myotatic (tendon) reflex.

Function: turns down activity so muscle does not over-contract

Name, describe, and draw the reflex that regulates:

muscle length
myotatic reflex

muscle tension
inverse myotatic reflex
Golgi tendon has 1b axon that acts as an inhibitory interneuron

limb withdrawal
withdrawal reflex
Describe each reflex for both extensor and flexor muscles.
Explain components and function of: muscle spindle, Golgi tendon organ.
Describe experiments that show function of intrafusal motor neuron in muscle
spindle function.
Concept: monosynaptic reflex loop.
Motor: central pathways

List and name the function of the two major descending pathways:
lateral:
o voluntary movements
ventromedial:
o balance and posture
Describe main functions of the two major pathways.
Ventromedial: balance and posture
Lateral: voluntary movements
What are effects of lesions in corticospinal tract?
Corticospinal tract: a bundle of axons that grows from the primary motor cortex that
goes to the spine

lesions in the corticospinal tract affects descending pathway,

specifically lateral pathway that controls voluntary movement
lateral pathway made up of corticospinal tract and rubrospinal tract
left side of brain affects right side of the body
stroke to the left side of the brain shows damage on the right side of the body
What are functions of the ventromedial pathways?
Balance
posture
Motor cortex: locate primary motor cortex, M1. Explain somatotopic map
(homunculus). Locate secondary motor areas.
List features of Parkinsons disease, and current treatments.
Parkinsons disease causes stiffness and uncontrollable tremors
o Slow, difficult movement
Affects basal ganglion loop (dopamine excitatory input)
Degeneration of dopaminergic receptors causes difficulty in execution of
movement
o Dopa can be given to patients to increases dopamine molecule
availability, which slows down further degeneration of dopamine
receptors in ventral midbrain
o Or, transplant dopamine-producing neurons or stem cells
How do M1 neurons code for movement? Explain population coding.
Movement encoded by collective activity of neurons
Activity from several neurons in M1 encodes force and direction of movement
o Direction of movement determined by getting average
Movement starts in primary motor cortex
Population coding: neuron responds most strongly to a stimulus near the
mean
Describe how population encoding of direction can be used for direct
cortical control of a robotic arm.
Describe Brain-Machine interface experiment in monkey or human.

Brain machine interface includes a grid of electrodes implanted into the

primary motor cortex of a monkey
Population coding allows for motor cortex control of a robotic arm by
producing an average of firing cells, which the brain-machine interface
implanted in the PCM translates into a command for the robotic limb. The
average allows the grid to determine which direction and movement to tell
the robot limb to do.

Programmed cell death in the nervous system. Dr. Tom Gould, Physiology,
SOM
Define programmed cell death.
The death of a cell in any form mediated by an intracellular program
Can occur in mass during development and during normal turnover of cells
(homeostasis) in adults
Explain the morphological characteristics of each, and the main causes or
triggers of each:
Apoptosis:
o DNA fragmentation
o intracellular signaling (caspases); fragmentation of cell into vesicles
o shrinkage and chromatin condensation (pykonis), budding, apoptotic
bodies phagocytosed by neighboring cells with no inflammation
o active response to injury; active self-destruction
o DNA damage can stimulate apoptosis
Necrosis: passive cell death
o Inflammation
o Release of proteolytic enzymes with inflammatory reaction
o Swelling
o bubbling with disruption of cell membrane
Autophagy:
o Decreased cell size
o Double membrane vesicles
o Degradation of organelles
o Double-membraned vesicles eat organelles and feed into lysosomes
o Vesicles include double membrane
Which form of cell death causes:
Inflammation:
o necrosis
DNA fragmentation:
o apoptosis
Phagocytosis:
o Autophagy
o apoptosis
Double membrane vesicles

o autophagy
DNA ladder
o apoptosis
TUNEL labeling
o apoptosis
Caspase activation
o apoptosis
Briefly explain glutamate excitotoxicity (high glut release, excess Ca
influx, necrosis)
Glutamate is released at synapse, usually transported away quickly
o When too much is released or slow removal:
o Ex. Hypoxia (low oxygen), hypoglycemia (low sugar), seizure,
neurodegeneration
Excessive calcium influx
o Calcium-dependent proteases
Induces necrosis
List three normal roles for cell death in development.

Phylogenetic disintegration of tissues that develop transiently

o Ex. vomeronasal organ (an organ we dont need anymore)
Morphogenetic sculpturing at regions of bending, folding etc.
o Ex. interdigital tissue (humans dont have webbing bc of PCD)
Histogenetic remodeling after an excessive period of production
o Ex. spinal motor neurons
What experiments in embryos show that peripheral targets (such as limb
tissue) regulates motor neuron survival? What is the evidence for
competition between neurons?
Experiments by Levi-Montalcini demonstrate that normal PCD and PCDinduced by loss of targets (Limb-Bud Removal) begin after proliferation and
differentiation
Peripheral targets regulate neuron numbers
o Removal of limb bud = less motor neurons
o Addition of limb bud = more motor neurons

Define:

neurotrophic hypothesis:
o we are born with more neurons than we need, so only those that
successfully make connections and trophic signals (needed for
survival) will stay, those that dont, die.
o Results in competition between neurons for target-derived trophic
(survival) molecules that are present in limiting amounts
o >50% undergo PCD
trophic molecules:
Trophic: promoting cellular growth, differentiation, and survival
What is the function of caspases in programed cell death?
Caspases trigger a cascade for programmed cell death to occur. If one pathway is
blocked, another caspase is activated for a different pathway of PCD to occur
List five neural diseases have increased cell death.
AIDS
Huntingtons
Parkinsons
Alzheimers
Downs Syndrome
Autism:
List the three main characteristics of autism.
Social and communication deficits
Restricted interests
Repetitive behavior
When do autistic symptoms typically first appear?
Within the first 1 to 3 years of life
What is prevalence of autism?
1 out of every 84 children
Slightly higher and more severe in boys
Compare concordance rates for identical and fraternal twins. How does
this comparison lead to an estimate of the genetic causes of autism?
Up to 60% of monozygotic twins are concordant with autistic behaviors, but 0% in
fraternal twins
Shows that there is strong genetic contribution to autism because monozygotic
twins have the same DNA versus different DNA in fraternal twins
What is the genetic evidence that autism may be caused by many different
but rare genetic abnormalities?
No consistent findings of shared genetic markers in people with autism
In incestuous families, no loci shared by and 2 of 80 families and no unique
deletions in 8 families
Specific genetic abnormalities cause small % of autism
Ex. Fragile X syndrome, Retts Syndrome
Summarize the evidence that childhood vaccines do not cause autism.

o
o

o
o

There is no way bacteria from the vaccines, which are very low in number compared
to the amount of bacteria was are constantly exposed to, could cause drastic
synaptic changes in the brain (commonly seen in patients with autism)
What not to miss on the final exam:
Problem solving:
circuits: neurons, genetic, cellular changes
reasoning with multiple steps
conditions that change, recall major experiments
Advice:
help from drawing out the circuit, cell pathway, anatomy?
Pay attention to precise terms in answer
Identify obvious fake answers
Where do CNS and PNS neurons come from?
Understanding CNS structure through development: Neural tube formation
Three layers: ecto, meso, endo
Ectoderm: forms tube = neurulation
Lateral inhibition: Notch-Delta signaling
Predictions from feedback loop. Would number of neurons increase or decrease?
Loss of function mutation in notch
High Notch signaling: constitutively active form of Notch
oncogenic
Loss of function mutation in Delta
If one cells is able to repress its neighbors more thoroughly, it will be able to
activate neurogenin and produce neuroD
Longitudinal pioneer axons are guided by a push-pull mechanism: when are
receptors active?
Growth cones for commissural axons first affect netrin1 receptors
Mechanism for sensitization
Ex. sea-slug: touch syphon, sensory neurons send signal to retract
Serotonin R increase cAMP increase PKA decrease K ion channels increase
NT release
Less K channels means elevated membrane polarization and more open calcium
channels open
Visual field deficits: where in the pathway