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GABA(A) and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II(i) PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization

Mechanical allodynia (pain to normally innocuous tactile stimuli) is a widespread symptom of inflammatory and neuropathic pain. Spinal or medullary dorsal horn (SDH or MDH) circuits mediating tactile sensation and pain need to interact in order to evoke mechanical allodynia. PKCγ-expressing (PKCγ(+)...

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Autores principales: El Khoueiry, Corinne, Alba-Delgado, Cristina, Antri, Myriam, Gutierrez-Mecinas, Maria, Todd, Andrew J., Artola, Alain, Dallel, Radhouane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033052/
https://www.ncbi.nlm.nih.gov/pubmed/35456035
http://dx.doi.org/10.3390/cells11081356
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author El Khoueiry, Corinne
Alba-Delgado, Cristina
Antri, Myriam
Gutierrez-Mecinas, Maria
Todd, Andrew J.
Artola, Alain
Dallel, Radhouane
author_facet El Khoueiry, Corinne
Alba-Delgado, Cristina
Antri, Myriam
Gutierrez-Mecinas, Maria
Todd, Andrew J.
Artola, Alain
Dallel, Radhouane
author_sort El Khoueiry, Corinne
collection PubMed
description Mechanical allodynia (pain to normally innocuous tactile stimuli) is a widespread symptom of inflammatory and neuropathic pain. Spinal or medullary dorsal horn (SDH or MDH) circuits mediating tactile sensation and pain need to interact in order to evoke mechanical allodynia. PKCγ-expressing (PKCγ(+)) interneurons and inhibitory controls within SDH/MDH inner lamina II (II(i)) are pivotal in connecting touch and pain circuits. However, the relative contribution of GABA and glycine to PKCγ(+) interneuron inhibition remains unknown. We characterized inhibitory inputs onto PKCγ(+) interneurons by combining electrophysiology to record spontaneous and miniature IPSCs (sIPSCs, mIPSCs) and immunohistochemical detection of GABA(A)Rα2 and GlyRα1 subunits in adult rat MDH. While GlyR-only- and GABA(A)R-only-mediated mIPSCs/sIPSCs are predominantly recorded from PKCγ(+) interneurons, immunohistochemistry reveals that ~80% of their inhibitory synapses possess both GABA(A)Rα2 and GlyRα1. Moreover, nearly all inhibitory boutons at gephyrin-expressing synapses on these cells contain glutamate decarboxylase and are therefore GABAergic, with around half possessing the neuronal glycine transporter (GlyT2) and therefore being glycinergic. Thus, while GABA and glycine are presumably co-released and GABA(A)Rs and GlyRs are present at most inhibitory synapses on PKCγ(+) interneurons, these interneurons exhibit almost exclusively GABA(A)R-only and GlyR-only quantal postsynaptic inhibitory currents, suggesting a pharmacological specialization of their inhibitory synapses.
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spelling pubmed-90330522022-04-23 GABA(A) and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II(i) PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization El Khoueiry, Corinne Alba-Delgado, Cristina Antri, Myriam Gutierrez-Mecinas, Maria Todd, Andrew J. Artola, Alain Dallel, Radhouane Cells Article Mechanical allodynia (pain to normally innocuous tactile stimuli) is a widespread symptom of inflammatory and neuropathic pain. Spinal or medullary dorsal horn (SDH or MDH) circuits mediating tactile sensation and pain need to interact in order to evoke mechanical allodynia. PKCγ-expressing (PKCγ(+)) interneurons and inhibitory controls within SDH/MDH inner lamina II (II(i)) are pivotal in connecting touch and pain circuits. However, the relative contribution of GABA and glycine to PKCγ(+) interneuron inhibition remains unknown. We characterized inhibitory inputs onto PKCγ(+) interneurons by combining electrophysiology to record spontaneous and miniature IPSCs (sIPSCs, mIPSCs) and immunohistochemical detection of GABA(A)Rα2 and GlyRα1 subunits in adult rat MDH. While GlyR-only- and GABA(A)R-only-mediated mIPSCs/sIPSCs are predominantly recorded from PKCγ(+) interneurons, immunohistochemistry reveals that ~80% of their inhibitory synapses possess both GABA(A)Rα2 and GlyRα1. Moreover, nearly all inhibitory boutons at gephyrin-expressing synapses on these cells contain glutamate decarboxylase and are therefore GABAergic, with around half possessing the neuronal glycine transporter (GlyT2) and therefore being glycinergic. Thus, while GABA and glycine are presumably co-released and GABA(A)Rs and GlyRs are present at most inhibitory synapses on PKCγ(+) interneurons, these interneurons exhibit almost exclusively GABA(A)R-only and GlyR-only quantal postsynaptic inhibitory currents, suggesting a pharmacological specialization of their inhibitory synapses. MDPI 2022-04-15 /pmc/articles/PMC9033052/ /pubmed/35456035 http://dx.doi.org/10.3390/cells11081356 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
El Khoueiry, Corinne
Alba-Delgado, Cristina
Antri, Myriam
Gutierrez-Mecinas, Maria
Todd, Andrew J.
Artola, Alain
Dallel, Radhouane
GABA(A) and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II(i) PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization
title GABA(A) and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II(i) PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization
title_full GABA(A) and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II(i) PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization
title_fullStr GABA(A) and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II(i) PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization
title_full_unstemmed GABA(A) and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II(i) PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization
title_short GABA(A) and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II(i) PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization
title_sort gaba(a) and glycine receptor-mediated inhibitory synaptic transmission onto adult rat lamina ii(i) pkcγ-interneurons: pharmacological but not anatomical specialization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033052/
https://www.ncbi.nlm.nih.gov/pubmed/35456035
http://dx.doi.org/10.3390/cells11081356
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