Chemogenetic synaptic silencing of neural circuits localizes a hypothalamus→midbrain pathway for feeding behavior.

ABSTRACT: Brain function is mediated by neural circuit connectivity, and elucidating the role of connections is aided by techniques to block their output. We developed cell-type-selective, reversible synaptic inhibition tools for mammalian neural circuits by leveraging G protein signaling pathways to suppress synaptic vesicle release. Here, we find that the pharmacologically selective designer Gi-protein-coupled receptor hM4D is a presynaptic silencer in the presence of its cognate ligand clozapine-N-oxide (CNO). Activation of hM4D signaling sharply reduced synaptic release probability and synaptic current amplitude. To demonstrate the utility of this tool for neural circuit perturbations, we developed an axon-selective hM4D-neurexin variant and used spatially targeted intracranial CNO injections to

SUBMITTER: Stachniak TJ 

PROVIDER: S-EPMC4306349 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature