Localisation and stress-induced plasticity of GABAA receptor subunits within the cellular networks of the mouse dorsal raphe nucleus

Nicole L. Corteen (Lead / Corresponding author), Jessica A. Carter, Uwe Rudolph, Delia Belelli, Jeremy J. Lambert, Jerome D. Swinny (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    The dorsal raphe nucleus (DRN) provides the major source of serotonin to the central nervous system (CNS) and modulates diverse neural functions including mood. Furthermore, DRN cellular networks are engaged in the stress-response at the CNS level allowing for adaptive behavioural responses, whilst stress-induced dysregulation of DRN and serotonin release is implicated in psychiatric disorders. Therefore, identifying the molecules regulating DRN activity is fundamental to understand DRN function in health and disease. GABA receptors (GABARs) allow for brain region, cell type and subcellular domain-specific GABA-mediated inhibitory currents and are thus key regulators of neuronal activity. Yet, the GABAR subtypes expressed within the neurochemically diverse cell types of the mouse DRN are poorly described. In this study, immunohistochemistry and confocal microscopy revealed that all serotonergic neurons expressed immunoreactivity for the GABAR alpha2 and 3 subunits, although the respective signals were co-localised to varying degrees with inhibitory synaptic marker proteins. Only a topographically located sub-population of serotonergic neurons exhibited GABAR alpha1 subunit immunoreactivity. However, all GABAergic as well as non-GABAergic, non-serotonergic neurons within the DRN expressed GABAR alpha1 subunit immunoreactivity. Intriguingly, immunoreactivity for the GABAR gamma2 subunit was enriched on GABAergic rather than serotonergic neurons. Finally, repeated restraint stress increased the expression of the GABAR alpha3 subunit at the mRNA and protein level. The study demonstrates the identity and location of distinct GABAR subunits within the cellular networks of the mouse DRN and that stress impacts on the expression levels of particular subunits at the gene and protein level.
    Original languageEnglish
    Pages (from-to)2739-2763
    Number of pages25
    JournalBrain Structure and Function
    Volume220
    Issue number5
    Early online date29 Jun 2014
    DOIs
    Publication statusPublished - Sep 2015

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