1. Network-level effects of optogenetic stimulation: experiment and simulation Cliff Kerr 1, Dan O'Shea 2, Werapong Goo 2, Salvador Dura-Bernal 1, Joe Francis 1, Ilka Diester 2, Paul Kalanithi 2, Karl Deisseroth 2, Krishna V. Shenoy 2, William W. Lytton 1 1 SUNY Downstate 2 Stanford University www.neurosimlab.org www.stanford.edu/~shenoy

2. 2/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Outline Methods – Optogenetics – Spiking network modeling Results – How does optogenetic stimulation influence network actvity – and vice versa? – How does optogenetic stimulation influence information flow?

3. 3/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Optogenetics Viral insertion of channelrhodopsin Neuronal activation and recording via optrode (electrode + optical fiber) New York Times, 2011 Adamantidis et al., Nature 2007 Wang et al., IEEE 2011

4. 4/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 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. 5/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Anatomy & physiology based on experimental data Generates realistic dynamics Adaptable to different brain regions (e.g. sensory, motor) Demonstrated control of virtual & robotic arms Neural equations: Spiking network model Chadderdon et al., PLOS ONE 2012

6. 6/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Spiking network model Connectivity matrix based on rat, cat, and macaque data Strong connectivity within each layer

7. 7/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Model dynamics

8. 8/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Optogenetic response

9. 9/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Optogenetic response

10. 10/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Optogenetic response

11. 11/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Response falls off as 1/r 2 from optrode Connectivity can explain firing rate heterogeneity Network-level effects Experiment Simulation

12. 12/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Granger causality Time series A Granger-causes B if A’s past helps predict B:

13. 13/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Stimulation reduces causality in  rhythm band (~10 Hz) Granger causality

14. 14/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 Causality is induced at stimulation frequency (~40 Hz) Granger causality

15. 15/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 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

16. 16/15 Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24 th, 2014 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 (experiments)