Brain Structure and Function

, Volume 220, Issue 5, pp 2739–2763 | Cite as

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

  • Nicole L. Corteen
  • Jessica A. Carter
  • Uwe Rudolph
  • Delia Belelli
  • Jeremy J. Lambert
  • Jerome D. SwinnyEmail author
Original Article


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. GABAA receptors (GABAARs) allow for brain region, cell type and subcellular domain-specific GABA-mediated inhibitory currents and are thus key regulators of neuronal activity. Yet, the GABAAR 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 GABAAR 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 GABAAR alpha1 subunit immunoreactivity. However, all GABAergic as well as non-GABAergic, non-serotonergic neurons within the DRN expressed GABAAR alpha1 subunit immunoreactivity. Intriguingly, immunoreactivity for the GABAAR gamma2 subunit was enriched on GABAergic rather than serotonergic neurons. Finally, repeated restraint stress increased the expression of the GABAAR alpha3 subunit at the mRNA and protein level. The study demonstrates the identity and location of distinct GABAAR 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.


Serotonin Immunohistochemistry Anxiety Benzodiazepine Depression 



We are extremely grateful to Professors Jean-Marc Fritschy and Werner Sieghart for the generous supply of antibodies against the various GABAAR subunits. We are also sincerely grateful to Scott Rodaway and Angela Scutt for their expert technical assistance.


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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Nicole L. Corteen
    • 1
  • Jessica A. Carter
    • 1
  • Uwe Rudolph
    • 2
  • Delia Belelli
    • 3
  • Jeremy J. Lambert
    • 3
  • Jerome D. Swinny
    • 1
    Email author
  1. 1.Institute for Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical SciencesUniversity of PortsmouthPortsmouthUK
  2. 2.Laboratory of Genetic Neuropharmacology, McLean Hospital and Department of PsychiatryHarvard Medical SchoolBelmontUSA
  3. 3.Division of Neuroscience, Medical Research InstituteNinewells Hospital and Medical School, Ninewells Hospital, Dundee UniversityDundeeUK

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