GABA<sub>A</sub> and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II<sub>i</sub> 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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MDPI AG
2022-04-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/8/1356 |
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| author | Corinne El Khoueiry Cristina Alba-Delgado Myriam Antri Maria Gutierrez-Mecinas Andrew J. Todd Alain Artola Radhouane Dallel |
| author_facet | Corinne El Khoueiry Cristina Alba-Delgado Myriam Antri Maria Gutierrez-Mecinas Andrew J. Todd Alain Artola Radhouane Dallel |
| author_sort | Corinne El Khoueiry |
| collection | DOAJ |
| 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<sup>+</sup>) interneurons and inhibitory controls within SDH/MDH inner lamina II (II<sub>i</sub>) are pivotal in connecting touch and pain circuits. However, the relative contribution of GABA and glycine to PKCγ<sup>+</sup> interneuron inhibition remains unknown. We characterized inhibitory inputs onto PKCγ<sup>+</sup> interneurons by combining electrophysiology to record spontaneous and miniature IPSCs (sIPSCs, mIPSCs) and immunohistochemical detection of GABA<sub>A</sub>Rα2 and GlyRα1 subunits in adult rat MDH. While GlyR-only- and GABA<sub>A</sub>R-only-mediated mIPSCs/sIPSCs are predominantly recorded from PKCγ<sup>+</sup> interneurons, immunohistochemistry reveals that ~80% of their inhibitory synapses possess both GABA<sub>A</sub>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<sub>A</sub>Rs and GlyRs are present at most inhibitory synapses on PKCγ<sup>+</sup> interneurons, these interneurons exhibit almost exclusively GABA<sub>A</sub>R-only and GlyR-only quantal postsynaptic inhibitory currents, suggesting a pharmacological specialization of their inhibitory synapses. |
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| last_indexed | 2024-03-09T11:01:22Z |
| publishDate | 2022-04-01 |
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| spelling | doaj.art-9af9cae2a5634251989ad7de05a50b482023-12-01T01:15:16ZengMDPI AGCells2073-44092022-04-01118135610.3390/cells11081356GABA<sub>A</sub> and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II<sub>i</sub> PKCγ-Interneurons: Pharmacological but Not Anatomical SpecializationCorinne El Khoueiry0Cristina Alba-Delgado1Myriam Antri2Maria Gutierrez-Mecinas3Andrew J. Todd4Alain Artola5Radhouane Dallel6Neuro-Dol, Inserm, Université Clermont Auvergne, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, FranceNeuro-Dol, Inserm, Université Clermont Auvergne, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, FranceNeuro-Dol, Inserm, Université Clermont Auvergne, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, FranceInstitute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UKInstitute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UKNeuro-Dol, Inserm, Université Clermont Auvergne, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, FranceNeuro-Dol, Inserm, Université Clermont Auvergne, CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, FranceMechanical 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<sup>+</sup>) interneurons and inhibitory controls within SDH/MDH inner lamina II (II<sub>i</sub>) are pivotal in connecting touch and pain circuits. However, the relative contribution of GABA and glycine to PKCγ<sup>+</sup> interneuron inhibition remains unknown. We characterized inhibitory inputs onto PKCγ<sup>+</sup> interneurons by combining electrophysiology to record spontaneous and miniature IPSCs (sIPSCs, mIPSCs) and immunohistochemical detection of GABA<sub>A</sub>Rα2 and GlyRα1 subunits in adult rat MDH. While GlyR-only- and GABA<sub>A</sub>R-only-mediated mIPSCs/sIPSCs are predominantly recorded from PKCγ<sup>+</sup> interneurons, immunohistochemistry reveals that ~80% of their inhibitory synapses possess both GABA<sub>A</sub>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<sub>A</sub>Rs and GlyRs are present at most inhibitory synapses on PKCγ<sup>+</sup> interneurons, these interneurons exhibit almost exclusively GABA<sub>A</sub>R-only and GlyR-only quantal postsynaptic inhibitory currents, suggesting a pharmacological specialization of their inhibitory synapses.https://www.mdpi.com/2073-4409/11/8/1356mechanical allodyniamedullary dorsal hornprotein kinase C gammainhibitory interneuronsspontaneous IPSCsminiature IPSCs |
| spellingShingle | Corinne El Khoueiry Cristina Alba-Delgado Myriam Antri Maria Gutierrez-Mecinas Andrew J. Todd Alain Artola Radhouane Dallel GABA<sub>A</sub> and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II<sub>i</sub> PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization Cells mechanical allodynia medullary dorsal horn protein kinase C gamma inhibitory interneurons spontaneous IPSCs miniature IPSCs |
| title | GABA<sub>A</sub> and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II<sub>i</sub> PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization |
| title_full | GABA<sub>A</sub> and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II<sub>i</sub> PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization |
| title_fullStr | GABA<sub>A</sub> and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II<sub>i</sub> PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization |
| title_full_unstemmed | GABA<sub>A</sub> and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II<sub>i</sub> PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization |
| title_short | GABA<sub>A</sub> and Glycine Receptor-Mediated Inhibitory Synaptic Transmission onto Adult Rat Lamina II<sub>i</sub> PKCγ-Interneurons: Pharmacological but Not Anatomical Specialization |
| title_sort | gaba sub a sub and glycine receptor mediated inhibitory synaptic transmission onto adult rat lamina ii sub i sub pkcγ interneurons pharmacological but not anatomical specialization |
| topic | mechanical allodynia medullary dorsal horn protein kinase C gamma inhibitory interneurons spontaneous IPSCs miniature IPSCs |
| url | https://www.mdpi.com/2073-4409/11/8/1356 |
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