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bioRxiv · 10.1101/2023.04.28.537363

Expression pattern of nicotinic acetylcholine receptor subunit transcripts in neurons and astrocytes in the ventral tegmental area and locus coeruleus

Gao, R.·Schneider, A. M.·Mulloy, S. M.·Lee, A. M.
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Abstract

Acetylcholine is the endogenous agonist for the neuronal nicotinic acetylcholine receptor (nAChR) system, which is involved in attention, memory, affective behaviors, and substance use disorders. Brain nAChRs are highly diverse with 11 different subunits that can form multiple receptor subtypes, each with distinct receptor and pharmacological properties. Different neuronal cell types can also express different nAChR subtypes, resulting in highly complex cholinergic signaling. Identifying which nAChR subunit transcripts are expressed in cell types can provide an indication of which nAChR combinations are possible and which receptor subtypes may be most pharmacologically relevant to target. In addition to differences in expression across cell types, nAChRs also undergo changes in expression levels from adolescence to adulthood. In this study, we used fluorescent in situ hybridization to identify and quantify the expression of 4, 5, 6, {beta}2 and {beta}3 nAChR subunit transcripts in dopaminergic, GABAergic, glutamatergic, and noradrenergic neurons and astrocytes in the ventral tegmental area (VTA) and locus coeruleus (LC) in adult and adolescent, male and female C57BL/6J mice. There were distinct differences in the pattern of nAChR subunit transcript expression between the two brain regions. LC noradrenergic neurons had high prevalence of 6, {beta}2 and {beta}3 expression, with very low expression of 4, suggesting the 6(non-4){beta}2{beta}3 receptor as a main subtype in these neurons. VTA astrocytes from adult mice showed greater prevalence of 5, 6, {beta}2 and {beta}3 transcript compared with adolescent mice. These data highlight the complex nAChR expression patterns across brain region and cell type.

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Gao, R., Schneider, A. M., Mulloy, S. M., Lee, A. M.. 2023-04-29. Expression pattern of nicotinic acetylcholine receptor subunit transcripts in neurons and astrocytes in the ventral tegmental area and locus coeruleus. https://doi.org/10.1101/2023.04.28.537363

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