Localisation of GABAA receptor ϵ-subunit in cholinergic and aminergic neurones and evidence for co-distribution with the θ-subunit in rat brain
Section snippets
Animals
Twelve normal adult male Wistar rats (400–450 g body weight; Iffa-Credo, l’Abresle, France) were kept under controlled lighting with free access to food and water. Tissue sections from one Macaca fascicularis monkey brain from a different study (Bezard et al., 2001) were also used. All animals were anaesthetised, operated, and killed in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC).
Immunohistochemistry
Eight rats were overdosed with 20% chloral hydrate and
General observations
The topographical distribution of ϵ-ir, obtained by the current immunofluorescence procedure, was identical to that previously obtained using the DAB–nickel-peroxidase technique (Moragues et al., 2000). However, resolution of cellular labelling was improved, appearing here as punctate elements (membranar and/or submembranar in the somatic and proximo-dendritic domains) rather than the patchy polymers of immunodeposited DAB.
Below follows a mapping study of the expression of ϵ-ir by monoamine- or
Discussion
This study shows that, although the GABAA receptor ϵ-subunit is expressed in restricted areas, it is present in numerous neuronal groups that project throughout the entire brain. Another striking feature of this study is the co-distribution of ϵ- and θ-subunit mRNAs in almost all areas studied, with the notable exception of the cholinergic nuclei, suggesting novel GABAA receptors. Functional implications of these new findings are discussed.
Conclusion
GABAA ϵ-subunit is expressed by many cholinergic, serotonergic and noradrenergic neurones and, to a lesser extent, dopaminergic cells. The α3-subunit is also known to be expressed in these neurones and the θ-subunit is probably expressed in aminergic neurones. We therefore propose that modulatory systems express novel GABAA receptors comprising at least α3/ϵ or α3/θ/ϵ subunits. These receptors probably have unique electrophysiological and pharmacological properties that may be relevant to the
Acknowledgements
This work was supported by CNRS, the University of Bordeaux 2 and the ‘Conseil Régional d’Aquitaine’. We would like to thank P. Lafon and S. Dovero for technical assistance and C. Gross and E. Bezard for monkey brain sections.
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