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Optogenetic control of three distinct dynamical regimes in bursting pyramidal neural networks via coordinated reset stimulation

Class project for Molecular engineering modeling (2009), taught by Michael Caplan

We present a biophysically realistic computer model of optogenetic stimulation by channelrhodopsin-2 in a network of bursting pyramidal neurons. Using this model, we have implemented a multisite coordinated reset algorithm to control bursting in the network and study the relationship between the kinetics of the ChR2 channel and the dynamics of pyramidal bursting.

The coordinated reset (CR) algorithm is based on the work of Tass et al (2009, Phys Rev E). Using this algorithm, seizure control is achieved by applying a series of staggered stimulus pulses, above, that sequentially reset the firing phases of four coupled neurons.

Coordinated reset stimulus pulses were applied optogenetically. Optogenetics refers to the novel suite of techniques that provides genetically targetable neural control in response to light stimulation. Here we use a computer model of channelrhodopsin-2 (ChR2) kinetics to explore the applicability of optogenetics to CR stimulation. The ChR2 kinetic model was implemented in GENESIS and compared to experimental data by Nikolic et al (2008). See above.

Coordinated reset simulationCoordinated reset simulation (click to stop)

Sample simulation showing breakup of synchrony by optogenetic coordinated reset stimulation.

We tested applying CR stimulation with a variety of pulse durations, ranging from 80msec to 8sec. We quantified the effectiveness of the protocol based on the reduction in the maximum extent of extracellular field emissions by the network. It was observed that optogenetic proteins could provide effective CR control well below the optimal pulse duration, which occurs when pulse duration is matched to the timescale of intrinsic neural bursting.

Simulations performed using GENESIS 2.3.

Last updated May 2011