Long-Term Depression of Striatal DA Release Induced by mGluRs via Sustained Hyperactivity of Local Cholinergic Interneurons

The cellular mechanisms regulating dopamine (DA) release in the striatum have attracted much interest in recent years. By in vitro amperometric recordings in mouse striatal slices, we show that a brief (5 min) exposure to the metabotropic glutamate receptor agonist DHPG (50 μM) induces a profound de...

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Autores principales:	Nicola B. Mercuri, Mauro Federici, Francesca Romana Rizzo, Lorenzo Maugeri, Sebastian L. D’Addario, Rossella Ventura, Nicola Berretta
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	dopamine LTD striatum cholinergic interneurons metabotropic glutamate receptors amperometry Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/34bbf5a0412348b482487d602f9dba65
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spelling	oai:doaj.org-article:34bbf5a0412348b482487d602f9dba652021-12-02T10:30:44ZLong-Term Depression of Striatal DA Release Induced by mGluRs via Sustained Hyperactivity of Local Cholinergic Interneurons1662-510210.3389/fncel.2021.798464https://doaj.org/article/34bbf5a0412348b482487d602f9dba652021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fncel.2021.798464/fullhttps://doaj.org/toc/1662-5102The cellular mechanisms regulating dopamine (DA) release in the striatum have attracted much interest in recent years. By in vitro amperometric recordings in mouse striatal slices, we show that a brief (5 min) exposure to the metabotropic glutamate receptor agonist DHPG (50 μM) induces a profound depression of synaptic DA release, lasting over 1 h from DHPG washout. This long-term depression is sensitive to glycine, which preferentially inhibits local cholinergic interneurons, as well as to drugs acting on nicotinic acetylcholine receptors and to the pharmacological depletion of released acetylcholine. The same DHPG treatment induces a parallel long-lasting enhancement in the tonic firing of presumed striatal cholinergic interneurons, measured with multi-electrode array recordings. When DHPG is bilaterally infused in vivo in the mouse striatum, treated mice display an anxiety-like behavior. Our results demonstrate that metabotropic glutamate receptors stimulation gives rise to a prolonged depression of the striatal dopaminergic transmission, through a sustained enhancement of released acetylcholine, due to the parallel long-lasting potentiation of striatal cholinergic interneurons firing. This plastic interplay between dopamine, acetylcholine, and glutamate in the dorsal striatum may be involved in anxiety-like behavior typical of several neuropsychiatric disorders.Nicola B. MercuriNicola B. MercuriMauro FedericiFrancesca Romana RizzoLorenzo MaugeriSebastian L. D’AddarioSebastian L. D’AddarioSebastian L. D’AddarioRossella VenturaRossella VenturaNicola BerrettaFrontiers Media S.A.articledopamineLTDstriatumcholinergic interneuronsmetabotropic glutamate receptorsamperometryNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Cellular Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dopamine LTD striatum cholinergic interneurons metabotropic glutamate receptors amperometry Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	dopamine LTD striatum cholinergic interneurons metabotropic glutamate receptors amperometry Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Nicola B. Mercuri Nicola B. Mercuri Mauro Federici Francesca Romana Rizzo Lorenzo Maugeri Sebastian L. D’Addario Sebastian L. D’Addario Sebastian L. D’Addario Rossella Ventura Rossella Ventura Nicola Berretta Long-Term Depression of Striatal DA Release Induced by mGluRs via Sustained Hyperactivity of Local Cholinergic Interneurons
description	The cellular mechanisms regulating dopamine (DA) release in the striatum have attracted much interest in recent years. By in vitro amperometric recordings in mouse striatal slices, we show that a brief (5 min) exposure to the metabotropic glutamate receptor agonist DHPG (50 μM) induces a profound depression of synaptic DA release, lasting over 1 h from DHPG washout. This long-term depression is sensitive to glycine, which preferentially inhibits local cholinergic interneurons, as well as to drugs acting on nicotinic acetylcholine receptors and to the pharmacological depletion of released acetylcholine. The same DHPG treatment induces a parallel long-lasting enhancement in the tonic firing of presumed striatal cholinergic interneurons, measured with multi-electrode array recordings. When DHPG is bilaterally infused in vivo in the mouse striatum, treated mice display an anxiety-like behavior. Our results demonstrate that metabotropic glutamate receptors stimulation gives rise to a prolonged depression of the striatal dopaminergic transmission, through a sustained enhancement of released acetylcholine, due to the parallel long-lasting potentiation of striatal cholinergic interneurons firing. This plastic interplay between dopamine, acetylcholine, and glutamate in the dorsal striatum may be involved in anxiety-like behavior typical of several neuropsychiatric disorders.
format	article
author	Nicola B. Mercuri Nicola B. Mercuri Mauro Federici Francesca Romana Rizzo Lorenzo Maugeri Sebastian L. D’Addario Sebastian L. D’Addario Sebastian L. D’Addario Rossella Ventura Rossella Ventura Nicola Berretta
author_facet	Nicola B. Mercuri Nicola B. Mercuri Mauro Federici Francesca Romana Rizzo Lorenzo Maugeri Sebastian L. D’Addario Sebastian L. D’Addario Sebastian L. D’Addario Rossella Ventura Rossella Ventura Nicola Berretta
author_sort	Nicola B. Mercuri
title	Long-Term Depression of Striatal DA Release Induced by mGluRs via Sustained Hyperactivity of Local Cholinergic Interneurons
title_short	Long-Term Depression of Striatal DA Release Induced by mGluRs via Sustained Hyperactivity of Local Cholinergic Interneurons
title_full	Long-Term Depression of Striatal DA Release Induced by mGluRs via Sustained Hyperactivity of Local Cholinergic Interneurons
title_fullStr	Long-Term Depression of Striatal DA Release Induced by mGluRs via Sustained Hyperactivity of Local Cholinergic Interneurons
title_full_unstemmed	Long-Term Depression of Striatal DA Release Induced by mGluRs via Sustained Hyperactivity of Local Cholinergic Interneurons
title_sort	long-term depression of striatal da release induced by mglurs via sustained hyperactivity of local cholinergic interneurons
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/34bbf5a0412348b482487d602f9dba65
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Long-Term Depression of Striatal DA Release Induced by mGluRs via Sustained Hyperactivity of Local Cholinergic Interneurons

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