The Evolution of the Optrode:

An Overview of in vivo Neuronal Modulation and

Recording
M. Andrews, I. Clark, & U. Zvi
Research Need Understand the activity of individual
neurons within a specific behavioral
context.

1. In vivo recording

2. Record from specified

neurons/population

3. Record with adequate

spatiotemporal resolution
Model Organism Mouse

● High throughput

● Easy to control experiments

● Genetic modification*
Barriers Engineering Design Specifications

● Heterogeneity of neurons

● Millisecond timescale of action

potentials

● Small size of model animals

○ Weight
○ Sterics
 Engineering Design Specifications

● Heterogeneity of neurons

● Millisecond timescale of action

potentials

● Small size of model animals

○ Weight
○ Sterics

Heterogeneity of neurons
Optogenetics Subtype Specific Neuromodulation

● Genetic modification
○ Insert light sensitive protein
○ Neuron subtype specific

● Bimodal modulation
○ Excite or inhibit cell
excitability

● Activated by light
○ No electrical
interference/noise
Heterogeneity of neurons
 Engineering Design Specifications
Heterogeneity of neurons

● Millisecond timescale of action

potentials

● Small size of model animals

○ Weight
○ Sterics

Millisecond timescale of
action potentials
Electrophysiology High Spatiotemporal Resolution

● Penetrating electrodes
○ Reach any brain region

● Electrode bundles
○ Allow for spatial
differentiation

● Instantaneous voltage changes

○ High temporal resolution

Millisecond timescale of
action potentials
Data Acquisition & ● Filtering
○ Low pass
Analysis ○ High pass

● Spike Sorting (Clustering)

○ Time dependent
○ Shape dependent

Millisecond timescale of
action potentials
 Engineering Design Specifications
Heterogeneity of neurons

Millisecond timescale of action

potentials

● Small size of model animals

○ Weight
○ Sterics

Small size of model animals

Head Mounted Freely Behaving

● Mount fibers and electrode

interface board (EIB) on mouse
head

● Conserve optical fiber and

electrodes in one fiber bundle or
silicon array

● Mouse can move freely

Small size of model animals

The Optrode

Combines ‘Op’tical control

with elec‘trode’ recording
during behavioral assays.
 2007

Evolution Overview

A decade of in vivo modulation 2010

and recording advances

2013

2017
2007
2007
2007
2007

Optic Fiber Diameter: 200 μm

2007
2010
2010
2010
2010
2010
2013
2013
2017
2017
2017
2017

Almost 400
channels, over
700 neurons
Future Direction Research

● Add optical controls to the silicon

probe of 2017 paper

● Incorporate multi-site recording to

investigate coordination dynamics
○ Reduction in size

Clinical Therapy

● Use as a closed loop therapeutic

○ Epilepsy?
References

Gradinaru, V., Thompson,K.R., Zhang, F., Mogri, M., Kay, K., Schneider, M.B., & Deisseroth, K. (2007).
Targeting and Read out Strategies for Fast Optical Neural Control In Vitro and In Vivo. J. Neurosci.
27(52):14231–14238.

Jun, J.J., et al. (2017). Fully integrated silicon probes for high-density recording of neural activity.Nature.
551(7679):232-236.

Royer,, S., Zemelman, B.V., Barbic, M., Losonczy, A., Buzsáki, G., & Magee, J.C. (2010). Multi-array silicon
probes with integrated optical fibers: light assisted perturbation and recording of local neural circuits in the
behaving animal. Eur J Neurosci. 31(12): 2279–2291.

Voigts, J., Siegle, J.H., Pritchett, D.L. & Moore, C.I. (2013). The flexDrive: an ultra-light implant for optical
control and highly parallel chronic recording of neuronal ensembles in freely moving mice. Front. Syst.
Neurosci. 7(8): 1662-5137.
Figure _: A) Activation of neurons
in SI region with ChR2. The site
of injection marked in orange; B)
Trace of an identified neuron on
one of the tetrodes for one
session.