The alpha2 nicotinic acetylcholine receptor, a subunit with unique and selective expression in inhibitory interneurons associated with principal cells

Markus M Hilscher; Sanja Mikulovic; Sharn Perry; Stina Lundberg; Klas Kullander

doi:10.1016/j.phrs.2023.106895

The alpha2 nicotinic acetylcholine receptor, a subunit with unique and selective expression in inhibitory interneurons associated with principal cells

Pharmacol Res. 2023 Oct:196:106895. doi: 10.1016/j.phrs.2023.106895. Epub 2023 Aug 29.

Authors

Markus M Hilscher¹, Sanja Mikulovic², Sharn Perry³, Stina Lundberg⁴, Klas Kullander⁵

Affiliations

¹ Department of Immunology, Genetics and Pathology, Uppsala University, IGP/BMC, Box 815, 751 08 Uppsala, Sweden; Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Solna, Sweden.
² Department of Immunology, Genetics and Pathology, Uppsala University, IGP/BMC, Box 815, 751 08 Uppsala, Sweden; Leibniz Institute for Neurobiology, Cognition & Emotion Laboratory, Magdeburg, Germany; German Center for Mental Health(DZPG), Germany.
³ Department of Immunology, Genetics and Pathology, Uppsala University, IGP/BMC, Box 815, 751 08 Uppsala, Sweden; Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Australia.
⁴ Department of Immunology, Genetics and Pathology, Uppsala University, IGP/BMC, Box 815, 751 08 Uppsala, Sweden.
⁵ Department of Immunology, Genetics and Pathology, Uppsala University, IGP/BMC, Box 815, 751 08 Uppsala, Sweden. Electronic address: klas.kullander@igp.uu.se.

PMID: 37652281
DOI: 10.1016/j.phrs.2023.106895

Abstract

Nicotinic acetylcholine receptors (nAChRs) play crucial roles in various human disorders, with the α7, α4, α6, and α3-containing nAChR subtypes extensively studied in relation to conditions such as Alzheimer's disease, Parkinson's disease, nicotine dependence, mood disorders, and stress disorders. In contrast, the α2-nAChR subunit has received less attention due to its more restricted expression and the scarcity of specific agonists and antagonists for studying its function. Nevertheless, recent research has shed light on the unique expression pattern of the Chrna2 gene, which encodes the α2-nAChR subunit, and its involvement in distinct populations of inhibitory interneurons. This review highlights the structure, pharmacology, localization, function, and disease associations of α2-containing nAChRs and points to the unique expression pattern of the Chrna2 gene and its role in different inhibitory interneuron populations. These populations, including the oriens lacunosum moleculare (OLM) cells in the hippocampus, Martinotti cells in the neocortex, and Renshaw cells in the spinal cord, share common features and contribute to recurrent inhibitory microcircuits. Thus, the α2-nAChR subunit's unique expression pattern in specific interneuron populations and its role in recurrent inhibitory microcircuits highlight its importance in various physiological processes. Further research is necessary to uncover the comprehensive functionality of α2-containing nAChRs, delineate their specific contributions to neuronal circuits, and investigate their potential as therapeutic targets for related disorders.

Keywords: Inhibitory interneuron; Martinotti cells; OLM cells; Renshaw cells; α2-nicotinic acetylcholine receptor.

Publication types

Review