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J Comp Neurol. 2022 Feb;530(3):607-626. doi: 10.1002/cne.25232. Epub 2021 Aug 19.

Morphological and neurochemical characterization of glycinergic neurons in laminae I-IV of the mouse spinal dorsal horn.

The Journal of comparative neurology

Camila Oliveira Miranda, Krisztina Hegedüs, Hendrik Wildner, Hanns Ulrich Zeilhofer, Miklós Antal

Affiliations

  1. Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  2. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
  3. Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland.

PMID: 34382691 DOI: 10.1002/cne.25232

Abstract

A growing body of experimental evidence shows that glycinergic inhibition plays vital roles in spinal pain processing. In spite of this, however, our knowledge about the morphology, neurochemical characteristics, and synaptic relations of glycinergic neurons in the spinal dorsal horn is very limited. The lack of this knowledge makes our understanding about the specific contribution of glycinergic neurons to spinal pain processing quite vague. Here we investigated the morphology and neurochemical characteristics of glycinergic neurons in laminae I-IV of the spinal dorsal horn using a GlyT2::CreERT2-tdTomato transgenic mouse line. Confirming previous reports, we show that glycinergic neurons are sparsely distributed in laminae I-II, but their densities are much higher in lamina III and especially in lamina IV. First in the literature, we provide experimental evidence indicating that in addition to neurons in which glycine colocalizes with GABA, there are glycinergic neurons in laminae I-II that do not express GABA and can thus be referred to as glycine-only neurons. According to the shape and size of cell bodies and dendritic morphology, we divided the tdTomato-labeled glycinergic neurons into three and six morphological groups in laminae I-II and laminae III-IV, respectively. We also demonstrate that most of the glycinergic neurons co-express neuronal nitric oxide synthase, parvalbumin, the receptor tyrosine kinase RET, and the retinoic acid-related orphan nuclear receptor β (RORβ), but there might be others that need further neurochemical characterization. The present findings may foster our understanding about the contribution of glycinergic inhibition to spinal pain processing.

© 2021 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.

Keywords: cell morphology; glycine transporter 2; glycinergic neurons; immunohistochemistry; mouse; spinal dorsal horn

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