@article {45167,
	title = {Chemogenetic synaptic silencing of neural circuits localizes a hypothalamus{\textrightarrow}midbrain pathway for feeding behavior.},
	journal = {Neuron},
	volume = {82},
	year = {2014},
	month = {2014 May 21},
	pages = {797-808},
	abstract = {<p>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 localize circuit connections from the hypothalamus to the midbrain responsible for feeding behavior. This synaptic silencing approach is broadly applicable for cell-type-specific and axon projection-selective functional analysis of diverse neural circuits.</p>
},
	keywords = {Agouti-Related Protein, Animals, Basic Helix-Loop-Helix Transcription Factors, Clozapine, Feeding Behavior, Humans, Hypothalamus, Membrane Potentials, Mesencephalon, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Molecular, Molecular Sequence Data, Nerve Net, Neural Inhibition, Neurons, Receptor, Muscarinic M4, Repressor Proteins, Rhodopsin, Time Factors},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2014.04.008},
	author = {Stachniak, Tevye J and Ghosh, Anirvan and Sternson, Scott M}
}
