| Literature DB >> 26606997 |
Wan-Chen Lin1, Ming-Chi Tsai1, Christopher M Davenport1, Caleb M Smith1, Julia Veit1, Neil M Wilson1, Hillel Adesnik2, Richard H Kramer3.
Abstract
Exogenously expressed opsins are valuable tools for optogenetic control of neurons in circuits. A deeper understanding of neural function can be gained by bringing control to endogenous neurotransmitter receptors that mediate synaptic transmission. Here we introduce a comprehensive optogenetic toolkit for controlling GABA(A) receptor-mediated inhibition in the brain. We developed a series of photoswitch ligands and the complementary genetically modified GABA(A) receptor subunits. By conjugating the two components, we generated light-sensitive versions of the entire GABA(A) receptor family. We validated these light-sensitive receptors for applications across a broad range of spatial scales, from subcellular receptor mapping to in vivo photo-control of visual responses in the cerebral cortex. Finally, we generated a knockin mouse in which the "photoswitch-ready" version of a GABA(A) receptor subunit genomically replaces its wild-type counterpart, ensuring normal receptor expression. This optogenetic pharmacology toolkit allows scalable interrogation of endogenous GABA(A) receptor function with high spatial, temporal, and biochemical precision.Entities:
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Year: 2015 PMID： 26606997 PMCID： PMC4775236 DOI： 10.1016/j.neuron.2015.10.026
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173