Network-level e ffects of optogenetic s timulation : experiment and simulation

Oscillations in the brain

Network-level effects of optogenetic stimulation: experiment and simulationCliff Kerr, Dan O'Shea, Werapong Goo, Salvador Dura-Bernal, Joe Francis, Ilka Diester, Paul Kalanithi, Karl Deisseroth, Krishna V. Shenoy, William W. LyttonNeurosimulation Laboratory, SUNY Downstate Medical Centerwww.neurosimlab.org

#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 20141OutlineMethodsHow does optogenetics work?How does a spiking network model work?ResultsHow does optogenetic stimulation influence network actvity and vice versa?How does optogenetic stimulation influence information flow?

#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 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#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 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#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 2014Anatomy & physiology based on experimental dataGenerates realistic dynamicsAdaptable to different brain regions (e.g. sensory, motor)Demonstrated control of virtual armNeural equations:Spiking network model

Chadderdon et al., PLOS ONE 2012#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 2014

Spiking network modelConnectivity matrix based on rat, cat, and macaque dataStrong connectivity within each layer#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 2014Model dynamics

#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 2014Optogenetic response 1

#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 2014Optogenetic response 2

#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 2014

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

Network-level effects

ExperimentSimulation#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 2014Granger causality: primerTime series A Granger-causes B if knowledge of As past helps predict B:

#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 2014Stimulation reduces causality in mu rhythm band (~10 Hz)Granger causality: results

#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 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 #/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 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(optogenetics)#/13Kerr et al. | Network-level effects of optogenetic stimulation | SUNY Research Day | April 2nd, 2014.14