title: Cholinergic interneurons mediate fast VGluT3-dependent glutamatergic transmission in the striatum.
abstract: The neurotransmitter glutamate is released by excitatory projection neurons throughout the brain. However, non-glutamatergic cells, including cholinergic and monoaminergic neurons, express markers that suggest that they are also capable of vesicular glutamate release. Striatal cholinergic interneurons (CINs) express the Type-3 vesicular glutamate transporter (VGluT3), although whether they form functional glutamatergic synapses is unclear. To examine this possibility, we utilized mice expressing Cre-recombinase under control of the endogenous choline acetyltransferase locus and conditionally expressed light-activated Channelrhodopsin2 in CINs. Optical stimulation evoked action potentials in CINs and produced postsynaptic responses in medium spiny neurons that were blocked by glutamate receptor antagonists. CIN-mediated glutamatergic responses exhibited a large contribution of NMDA-type glutamate receptors, distinguishing them from corticostriatal inputs. CIN-mediated glutamatergic responses were insensitive to antagonists of acetylcholine receptors and were not seen in mice lacking VGluT3. Our results indicate that CINs are capable of mediating fast glutamatergic transmission, suggesting a new role for these cells in regulating striatal activity.
authors.affiliation: Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Higley
authors.forename: Aryn H
authors.initials: AH
authors.lastname: Gittis
authors.forename: Ian A
authors.initials: IA
authors.lastname: Oldenburg
authors.forename: Nina
authors.initials: N
authors.lastname: Balthasar
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Seal
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.forename: Anatol C
authors.initials: AC
authors.lastname: Kreitzer
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Sabatini
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D000075402:Channelrhodopsins; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D010852:Picrotoxin / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D000697:Central Nervous System Stimulants; D000075402:Channelrhodopsins; D008464:Mecamylamine; D010852:Picrotoxin; D011950:Receptors, Cholinergic; D016194:Receptors, N-Methyl-D-Aspartate; D012601:Scopolamine; C504941:Slc17a8 protein, mouse