1. Network-level effects of optogenetic stimulation: experiment and simulation
Cliff Kerr, Dan O'Shea, Werapong Goo, Salvador Dura-Bernal, Joe Francis, Ilka Diester, Paul Kalanithi, Karl Deisseroth, Krishna V. Shenoy, William W. Lytton
Neurosimulation Laboratory, SUNY Downstate Medical Center

2. Outline Methods Results How does optogenetics work?
How does a spiking network model work?
Results
How does optogenetic stimulation influence network actvity – and vice versa?
How does optogenetic stimulation influence information flow?

3. Optogenetics Viral insertion of channelrhodopsin
Neuronal activation and recording via optrode (electrode + optical fiber)
New York Times, 2011
Wang et al., IEEE 2011
Adamantidis et al., Nature 2007

4. Spiking network model 6-layered cortex
Izhikevich (integrate-and-fire) neurons
4 types of neuron: regular or bursting (excitatory), fast or low-threshold (inhibitory)
24,800 neurons total
Kerr et al.,
Frontiers 2014

5. Spiking network model Anatomy & physiology based on experimental data
Generates realistic dynamics
Adaptable to different brain regions (e.g. sensory, motor)
Demonstrated control of virtual arm
Chadderdon et al., PLOS ONE 2012
Neural equations:
𝑑𝑉 𝑑𝑡 =0.04 𝑉 2 +5𝑉+140−𝑈+𝐼
𝑑𝑈 𝑑𝑡 =𝑎(𝑏𝑉−𝑈)
if 𝑉≥30 mV: 𝑉←𝑐 𝑈←𝑑

6. Spiking network model
Connectivity matrix based on rat, cat, and macaque data
Strong connectivity within each layer

7. Model dynamics

8. Optogenetic response 1

9. Optogenetic response 2

10. Network-level effects
Response falls off as 1/r2 from optrode
Connectivity can explain firing rate heterogeneity
Simulation
Experiment

11. Granger causality: primer
Time series A Granger-causes B if knowledge of A’s past helps predict B:

12. Granger causality: results
Stimulation reduces causality in mu rhythm band (~10 Hz)

13. Summary First network model of optogenetics
Synaptic connections determine the network’s response to optogenetic stimulation
Optogenetic stimulation may be used to modulate information flow
Future work: predicting the effects of specific stimulation protocols

14. Acknowledgements
Daniel J. O'Shea (experiments) Salvador Dura-Bernal (modeling) Ilka Diester (optogenetics) Karl Deisseroth (optogenetics) William W. Lytton (modeling)
Werapong Goo (experiments)
Joseph T. Francis (modeling)
Paul Kalanithi (optogenetics)
Krishna V. Shenoy (optogenetics) .