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Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord

During perinatal development, corticospinal tract (CST) projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts...

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Autores principales: Russ, Jeffrey B., Verina, Tatyana, Comer, John D., Comi, Anne M., Kaltschmidt, Julia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782692/
https://www.ncbi.nlm.nih.gov/pubmed/24093008
http://dx.doi.org/10.3389/fncir.2013.00150
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author Russ, Jeffrey B.
Verina, Tatyana
Comer, John D.
Comi, Anne M.
Kaltschmidt, Julia A.
author_facet Russ, Jeffrey B.
Verina, Tatyana
Comer, John D.
Comi, Anne M.
Kaltschmidt, Julia A.
author_sort Russ, Jeffrey B.
collection PubMed
description During perinatal development, corticospinal tract (CST) projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts specific aspects of spinal circuit development, particularly the inhibitory microcircuitry that regulates spinal reflex circuits. In this study, we sought to determine how ischemic cortical damage impacts the synaptic attributes of a well-characterized population of inhibitory, GABAergic interneurons, called GABApre neurons, which modulates the efficiency of proprioceptive sensory terminals in the sensorimotor reflex circuit. We found that putative GABApre interneurons receive CST input and, using an established mouse model of perinatal stroke, that cortical ischemic injury results in a reduction of CST density within the intermediate region of the spinal cord, where these interneurons reside. Importantly, CST alterations were restricted to the side contralateral to the injury. Within the synaptic terminals of the GABApre interneurons, we observed a dramatic upregulation of the 65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65). In accordance with the CST density reduction, GAD65 was elevated on the side of the spinal cord contralateral to cortical injury. This effect was not seen for other GABApre synaptic markers or in animals that received sham surgery. Our data reveal a novel effect of perinatal stroke that involves severe deficits in the architecture of a descending spinal pathway, which in turn appear to promote molecular alterations in a specific spinal GABAergic circuit.
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spelling pubmed-37826922013-10-03 Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord Russ, Jeffrey B. Verina, Tatyana Comer, John D. Comi, Anne M. Kaltschmidt, Julia A. Front Neural Circuits Neuroscience During perinatal development, corticospinal tract (CST) projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts specific aspects of spinal circuit development, particularly the inhibitory microcircuitry that regulates spinal reflex circuits. In this study, we sought to determine how ischemic cortical damage impacts the synaptic attributes of a well-characterized population of inhibitory, GABAergic interneurons, called GABApre neurons, which modulates the efficiency of proprioceptive sensory terminals in the sensorimotor reflex circuit. We found that putative GABApre interneurons receive CST input and, using an established mouse model of perinatal stroke, that cortical ischemic injury results in a reduction of CST density within the intermediate region of the spinal cord, where these interneurons reside. Importantly, CST alterations were restricted to the side contralateral to the injury. Within the synaptic terminals of the GABApre interneurons, we observed a dramatic upregulation of the 65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65). In accordance with the CST density reduction, GAD65 was elevated on the side of the spinal cord contralateral to cortical injury. This effect was not seen for other GABApre synaptic markers or in animals that received sham surgery. Our data reveal a novel effect of perinatal stroke that involves severe deficits in the architecture of a descending spinal pathway, which in turn appear to promote molecular alterations in a specific spinal GABAergic circuit. Frontiers Media S.A. 2013-09-25 /pmc/articles/PMC3782692/ /pubmed/24093008 http://dx.doi.org/10.3389/fncir.2013.00150 Text en Copyright © Russ, Verina, Comer, Comi and Kaltschmidt. 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
Russ, Jeffrey B.
Verina, Tatyana
Comer, John D.
Comi, Anne M.
Kaltschmidt, Julia A.
Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord
title Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord
title_full Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord
title_fullStr Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord
title_full_unstemmed Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord
title_short Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord
title_sort corticospinal tract insult alters gabaergic circuitry in the mammalian spinal cord
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782692/
https://www.ncbi.nlm.nih.gov/pubmed/24093008
http://dx.doi.org/10.3389/fncir.2013.00150
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