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Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

Golgi cells (GoCs) are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generat...

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Autores principales: Botta, Paolo, Zucca, Aya, Valenzuela, C. Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915290/
https://www.ncbi.nlm.nih.gov/pubmed/24567705
http://dx.doi.org/10.3389/fnint.2014.00010
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author Botta, Paolo
Zucca, Aya
Valenzuela, C. Fernando
author_facet Botta, Paolo
Zucca, Aya
Valenzuela, C. Fernando
author_sort Botta, Paolo
collection PubMed
description Golgi cells (GoCs) are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABA(A) receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2)-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM) reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na(+)/K(+) pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABA(A) receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex.
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spelling pubmed-39152902014-02-24 Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input Botta, Paolo Zucca, Aya Valenzuela, C. Fernando Front Integr Neurosci Neuroscience Golgi cells (GoCs) are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABA(A) receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2)-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM) reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na(+)/K(+) pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABA(A) receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex. Frontiers Media S.A. 2014-02-06 /pmc/articles/PMC3915290/ /pubmed/24567705 http://dx.doi.org/10.3389/fnint.2014.00010 Text en Copyright © 2014 Botta, Zucca and Valenzuela. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Botta, Paolo
Zucca, Aya
Valenzuela, C. Fernando
Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input
title Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input
title_full Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input
title_fullStr Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input
title_full_unstemmed Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input
title_short Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input
title_sort acute ethanol exposure inhibits silencing of cerebellar golgi cell firing induced by granule cell axon input
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915290/
https://www.ncbi.nlm.nih.gov/pubmed/24567705
http://dx.doi.org/10.3389/fnint.2014.00010
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