title: Novel fast adapting interneurons mediate cholinergic-induced fast GABAA inhibitory postsynaptic currents in striatal spiny neurons.
abstract: Previous work suggests that neostriatal cholinergic interneurons control the activity of several classes of GABAergic interneurons through fast nicotinic receptor-mediated synaptic inputs. Although indirect evidence has suggested the existence of several classes of interneurons controlled by this mechanism, only one such cell type, the neuropeptide-Y-expressing neurogliaform neuron, has been identified to date. Here we tested the hypothesis that in addition to the neurogliaform neurons that elicit slow GABAergic inhibitory responses, another interneuron type exists in the striatum that receives strong nicotinic cholinergic input and elicits conventional fast GABAergic synaptic responses in projection neurons. We obtained in vitro slice recordings from double transgenic mice in which Channelrhodopsin-2 was natively expressed in cholinergic neurons and a population of serotonin receptor-3a-Cre-expressing GABAergic interneurons were visualized with tdTomato. We show that among the targeted GABAergic interneurons a novel type of interneuron, termed the fast-adapting interneuron, can be identified that is distinct from previously known interneurons based on immunocytochemical and electrophysiological criteria. We show using optogenetic activation of cholinergic inputs that fast-adapting interneurons receive a powerful supra-threshold nicotinic cholinergic input in vitro. Moreover, fast adapting neurons are densely connected to projection neurons and elicit fast, GABAA receptor-mediated inhibitory postsynaptic current responses. The nicotinic receptor-mediated activation of fast-adapting interneurons may constitute an important mechanism through which cholinergic interneurons control the activity of projection neurons and perhaps the plasticity of their synaptic inputs when animals encounter reinforcing or otherwise salient stimuli.
authors: Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey, 197 University Avenue, Newark, NJ, 07102, USA.
authors: Thomas W
authors: TW
authors: Faust
authors: Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey, 197 University Avenue, Newark, NJ, 07102, USA.
authors: Maxime
authors: M
authors: Assous
authors: Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey, 197 University Avenue, Newark, NJ, 07102, USA.
authors: Fulva
authors: F
authors: Shah
authors: Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey, 197 University Avenue, Newark, NJ, 07102, USA.
authors: James M
authors: JM
authors: Tepper
authors: Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey, 197 University Avenue, Newark, NJ, 07102, USA.
authors: Tibor
authors: T
authors: Koós
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D000075402:Channelrhodopsins; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D005215:Fasting / Q000502:physiology*; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D020955:Striatonigral Degeneration; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D018678:Cholinergic Agents; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D004079:Dihydro-beta-Erythroidine; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase
keywords: acetylcholine; fast inhibition; mouse; neostriatum; nicotinic receptors