title: Striatal cholinergic interneurons Drive GABA release from dopamine terminals.
abstract: Striatal cholinergic interneurons are implicated in motor control, associative plasticity, and reward-dependent learning. Synchronous activation of cholinergic interneurons triggers large inhibitory synaptic currents in dorsal striatal projection neurons, providing one potential substrate for control of striatal output, but the mechanism for these GABAergic currents is not fully understood. Using optogenetics and whole-cell recordings in brain slices, we find that a large component of these inhibitory responses derive from action-potential-independent disynaptic neurotransmission mediated by nicotinic receptors. Cholinergically driven IPSCs were not affected by ablation of striatal fast-spiking interneurons but were greatly reduced after acute treatment with vesicular monoamine transport inhibitors or selective destruction of dopamine terminals with 6-hydroxydopamine, indicating that GABA release originated from dopamine terminals. These results delineate a mechanism in which striatal cholinergic interneurons can co-opt dopamine terminals to drive GABA release and rapidly inhibit striatal output neurons.
authors.affiliation: The Gladstone Institutes, San Francisco, CA, 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Alexandra B
authors.initials: AB
authors.lastname: Nelson
authors.affiliation: The Gladstone Institutes, San Francisco, CA, 94158, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Hammack
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Cindy F
authors.initials: CF
authors.lastname: Yang
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Nirao M
authors.initials: NM
authors.lastname: Shah
authors.affiliation: Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Seal
authors.affiliation: The Gladstone Institutes, San Francisco, CA, 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: akreitzer@gladstone.ucsf.edu.
authors.forename: Anatol C
authors.initials: AC
authors.lastname: Kreitzer
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000075402:Channelrhodopsins; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D003342:Corpus Striatum / Q000166:cytology*; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000075402:Channelrhodopsins; C583261:Drd1 protein, mouse; D018377:Neurotransmitter Agents; D010320:Parvalbumins; D026902:Potassium Channel Blockers; D017447:Receptors, Dopamine D1; D026941:Sodium Channel Blockers; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D004298:Dopamine