GABA_A and glycine receptor-mediated inhibitory synaptic transmission onto adult rat lamina IIi PKCγ-interneurons: pharmacological but not anatomical specialization

El Khoueiry, C., Alba-Delgado, C., Antri, M., Gutierrez-Mecinas, M. , Todd, A. J. , Artola, A. and Dallel, R. (2022) GABA_A and glycine receptor-mediated inhibitory synaptic transmission onto adult rat lamina IIi PKCγ-interneurons: pharmacological but not anatomical specialization. Cells, 11(8), 1356. (doi: 10.3390/cells11081356) (PMID:35456035) (PMCID:PMC9033052)

Abstract

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 ) 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 Rα2 and GlyRα1 subunits in adult rat MDH. While GlyR-only- and GABA R-only-mediated mIPSCs/sIPSCs are predominantly recorded from PKCγ interneurons, immunohistochemistry reveals that ~80% of their inhibitory synapses possess both GABA 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 Rs and GlyRs are present at most inhibitory synapses on PKCγ interneurons, these interneurons exhibit almost exclusively GABA R-only and GlyR-only quantal postsynaptic inhibitory currents, suggesting a pharmacological specialization of their inhibitory synapses.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gutierrez-Mecinas, Dr Maria and Todd, Professor Andrew

Creator Roles

Gutierrez-Mecinas, M.: Investigation, Formal analysis, Visualization
Todd, A. J.: Conceptualization, Methodology, Formal analysis, Visualization, Supervision, Writing – original draft, Writing – review and editing, Project administration, Funding acquisition

• Authors: El Khoueiry, C., Alba-Delgado, C., Antri, M., Gutierrez-Mecinas, M., Todd, A. J., Artola, A., and Dallel, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Cells
• Publisher: MDPI
• ISSN: 2073-4409
• ISSN (Online): 2073-4409
• Published Online: 15 April 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Cells 11(8): 1356
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
308174		Spinal circuits underlying pathological pain	Andrew Todd	Wellcome Trust (WELLCOTR)	219433/Z/19/Z	Centre for Neuroscience