期刊
NEURON
卷 88, 期 5, 页码 879-891出版社
CELL PRESS
DOI: 10.1016/j.neuron.2015.10.026
关键词
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资金
- National Institutes of Health [U01 NS090527, P30 EY003176, PN2 EY018241, 1R01EY023756-01]
- Swiss National Foundation [P2FRP3_155172]
- Swiss National Science Foundation (SNF) [P2FRP3_155172] Funding Source: Swiss National Science Foundation (SNF)
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 photo-switch 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 photocontrol 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.
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