title: KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons.
abstract: Striatal projection neurons (SPNs) process motor and cognitive information. Their activity is affected by Parkinson's disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is the KV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulating KV7 channels. We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, DF, Mexico.
authors.forename: M Belén
authors.initials: MB
authors.lastname: Pérez-Ramírez
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, DF, Mexico.
authors.forename: Antonio
authors.initials: A
authors.lastname: Laville
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, DF, Mexico.
authors.forename: Dagoberto
authors.initials: D
authors.lastname: Tapia
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, DF, Mexico.
authors.forename: Mariana
authors.identifier: 0000-0001-9987-6704
authors.initials: M
authors.lastname: Duhne
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, DF, Mexico.
authors.forename: Esther
authors.initials: E
authors.lastname: Lara-González
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, DF, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Bargas
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, DF, Mexico.
authors.forename: Elvira
authors.initials: E
authors.lastname: Galarraga
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology; D059329:Cholinergic Neurons / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D051656:KCNQ Potassium Channels / Q000502:physiology*; D008822:Mice, Transgenic; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D043643:Receptor, Muscarinic M1 / Q000819:agonists / Q000037:antagonists & inhibitors; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D051656:KCNQ Potassium Channels; C506326:KCNQ5 channel, mouse; C496907:MT-7 mamba toxin; D018721:Muscarinic Agonists; D010455:Peptides; D043643:Receptor, Muscarinic M1; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D009116:Muscarine