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Expression profiling by high throughput sequencing Summary The cbat, an ancient small brain area in the epithalamus, densely expresses nicotinic acetylcholine receptors and is chwt for nicotine intake and aversion. As such, identification of strategies to manipulate habenular activity chay yield new approaches to treat nicotine addiction. Here we show that GPR, an orphan G protein-coupled receptor GPCR highly enriched in the habenula of humans and rodents is expressed at presynaptic membranes and synaptic vesicles, and associates with synaptic components controlling vesicle release and ion transport. Deletion of Gpr inhibits evoked neurotransmission but enhances spontaneous miniature synaptic currents geo chat eliminates short-term plasticity induced by nicotine. GprKO mice show diminished behavioral responses to nicotine, and self-administer greater quantities geo chat the drug, phenotypes rescued by viral re-expression of Gpr in the habenula.
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