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.

Oscillations in the brain

Network-level effects of optogenetic stimulation: experiment and simulationCliff Kerr1, Dan O'Shea2, Werapong Goo2, Salvador Dura-Bernal1, Joe Francis1, Ilka Diester2, Paul Kalanithi2, Karl Deisseroth2, Krishna V. Shenoy2, William W. Lytton1 1 SUNY Downstate 2 Stanford University www.neurosimlab.org www.stanford.edu/~shenoy

#/15Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24th, 20141OutlineMethodsOptogeneticsSpiking network modelingResultsHow does optogenetic stimulation influence network actvity and vice versa?How does optogenetic stimulation influence information flow?

#/15Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24th, 2014OptogeneticsViral insertion of channelrhodopsin Neuronal activation and recording via optrode (electrode + optical fiber)

New York Times, 2011Adamantidis et al., Nature 2007

Wang et al., IEEE 2011#/15Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24th, 2014Spiking network model

6-layered cortexIzhikevich (integrate-and-fire) neurons4 types of neuron: regular or bursting (excitatory), fast or low-threshold (inhibitory)24,800 neurons totalKerr et al., Frontiers 2014#/15Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24th, 2014Anatomy & physiology based on experimental dataGenerates realistic dynamicsAdaptable to different brain regions (e.g. sensory, motor)Demonstrated control of virtual & robotic armsNeural equations:Spiking network model

Chadderdon et al., PLOS ONE 2012#/15Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24th, 2014

Spiking network modelConnectivity matrix based on rat, cat, and macaque dataStrong connectivity within each layer#/15Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24th, 2014Model dynamics

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

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

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

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

Response falls off as 1/r2 from optrodeConnectivity can explain firing rate heterogeneity

Network-level effects

ExperimentSimulation#/15Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24th, 2014Granger causalityTime series A Granger-causes B if As past helps predict B:

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

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

#/15Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24th, 2014SummaryFirst network model of optogeneticsSynaptic connections determine the networks response to optogenetic stimulationOptogenetic stimulation may be used to modulate information flowFuture work: predicting the effects of specific stimulation protocols #/15Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24th, 2014

AcknowledgementsDaniel 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)#/15Kerr et al. | Network-level effects of optogenetic stimulation | NCM | April 24th, 2014.16