Viral strategies for bi-directional optogenetic control of specific cell types in neocortex of non-transgenic animals

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Project Summary Here we propose to develop a novel rabies virus based strategy to express two channelrhodopsin proteins independent manipulation of excitatory and inhibitory transmembrane potentials in the same population of neurons. Combined with the use of cell-type specific promoters in helper viruses and rabies pseudotyping, the new suite of viruses will enable full control of excitation and inhibition over specific neural network subtypes of non-transgenic animals. We will apply the new technique here to determine cell type specific contributions of feedforward cortical integration on the emergence of complex visual feature selectivity using highly visual animal models. While our goal is primarily to develop this novel method to study structure-function organization of visual cortex, this technique will be readily applicable to study any brain region. Our proposed technique combines recently available channelrhodopsin cation and anion channel with our recently our developed viral strategies for accessing specific cell types and specific circuits in non- transgenic species (Liu et al., 2013, Curr Biol) opening the door for unprecedented fine scale study of structure-function relationships in highly visual mammals. For this proposal we will apply these new strategies to enable optogenetic manipulation of specific cell types involved in higher order visual cortex receptive field formation. These studies will represent the most direct in vivo assessment of inhibitory neurons and underlying intra- and inter-laminar circuitry of a large, highly visual mammal, advancing our understanding of how basic visual processes arise and depend on complex cortical structure.