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Computational models of optogenetic tools for controlling neural circuits with light

Optogenetics is a new neurotechnology innovation based on the creation of light sensitivity of neurons using gene technologies and remote light activation. Optogenetics allows for the first time straightforward targeted neural stimulation with practically no interference between multiple stimulation points since either light beam can be finely confined or the expression of light sensitive ion channels and pumps can be genetically targeted. Here we present a generalised computational modeling technique for various types of optogenetic mechanisms, which was implemented in the NEURON simulation environment. It was demonstrated on the example of a two classical mechanisms for cells optical activation and silencing: channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR).We theoretically investigate the dynamics of the neural response of a layer 5 cortical pyramidal neuron (L5) to four different types of illuminations: 1) wide-field whole cell illumination 2) wide-field apical dendritic illumination 3) focal somatic illumination and 4) focal axon initial segment (AIS) illumination. We show that whole-cell illumination of halorhodopsin most effectively hyperpolarizes the neuron and is able to silence the cell even when driving input is present. However, when channelrhodopsin-2 and halorhodopsin are concurrently active, the relative location of each illumination determines whether the response is modulated with a balance towards depolarization. The methodology developed in this study will be significant to interpret and design optogenetic experiments and in the field of neuroengineering in general.