Elsevier

Neuroscience

Volume 102, Issue 3, 5 February 2001, Pages 625-638
Neuroscience

Expression of GABAA receptor subunits in rat brainstem auditory pathways: cochlear nuclei, superior olivary complex and nucleus of the lateral lemniscus

https://doi.org/10.1016/S0306-4522(00)00525-XGet rights and content

Abstract

Inhibition by GABA is important for auditory processing, but any adaptations of the ionotropic type A receptors are unknown. Here we describe, using in situ hybridization, the subunit expression patterns of GABAA receptors in the rat cochlear nucleus, superior olivary complex, and dorsal and ventral nuclei of the lateral lemniscus. All neurons express the β3 and γ2L subunit messenger RNAs, but use different α subunits. In the dorsal cochlear nucleus, fusiform (pyramidal) and giant cells express α1, α3, β3 and γ2L. Dorsal cochlear nucleus interneurons, particularly vertical or tuberculoventral cells and cartwheel cells, express α3, β3 and γ2L. In the ventral cochlear nucleus, octopus cells express α1, β3, γ2L and δ. Spherical cells express α1, α3, α5, β3 and γ2L. In the superior olivary complex, the expression profile is α3, α5, β3 and γ2L. Both dorsal and ventral cochlear nucleus granule cells express α1, α6, β3 and γ2L; unlike their cerebellar granule cell counterparts, they do not express β2, γ2S or the δ subunit genes. The δ subunit's absence from cochlear nucleus granule cells may mean that tonic inhibition mediated by extrasynaptic GABAA receptors is less important for this cell type. In both the dorsal and ventral nuclei of the lateral lemniscus, α1, β3 and γ2L are the main subunit messenger RNAs; the ventral nucleus also expresses the δ subunit.

We have mapped, using in situ hybridization, the subunit expression patterns of the GABAA receptor in the auditory brainstem nuclei. In contrast to many brain regions, the β2 subunit gene and γ2S splice forms are not highly expressed in auditory brainstem nuclei. GABAA receptors containing β3 and γ2L may be particularly well suited to auditory processing, possibly because of the unique phosphorylation profile of this subunit combination.

Section snippets

Experimental procedures

To produce the atlas, we used nine adult male rats (Wistar, weights between 250 and 350 g) from the Miguel Hernández University Animal House. Care and handling of the animals followed European Union regulations, and were approved and supervised by the University Animal House. All efforts were made to minimize animal suffering and to use only the number of animals necessary to produce reliable scientific data.

In situ hybridization was as described.78 To analyse the distribution of all receptor

Results

To confirm probe specificity, coronal sections from the forebrain and cerebellum/brainstem were hybridized with oligonucleotide probes specific for the GABAA receptor α1–α6, β1–β3, γ1, γ2L and γ2S, γ3, and δ subunit mRNAs. Each probe gave a characteristic hybridization pattern identical with previous reports33., 40., 52., 77. (data not shown). The probes were hybridized to a set of coronal sections containing the CN, SOC and NLL. The results are summarized in Fig. 3, Fig. 6, Fig. 9, and Table 1

Discussion

GABAergic signalling is important for auditory processing.3., 14., 20., 35., 41., 44. Auditory brainstem neurons have demanding requirements placed on them: some cell types must match the high-frequency signals in the auditory nerve, otherwise information will be lost; on the other hand, other cell types do not fire in direct proportion to auditory input. We were interested in seeing if there was a correlation between GABAA receptor subunit expression and cell type. We mapped, using in situ

Conclusions

With the exception of γ1 subunit gene expression in a small neuronal population (probably stellate interneurons) in the DCN, almost every cell type in the brainstem auditory pathways uses the γ2L splice version of the γ2 gene and the β3 subunit gene, together with different α subunits. The αnβ3γ2L receptors may be particularly well suited to auditory processing requirements.

Acknowledgements

D.M. held a European Union TMR Fellowship (Category 30); M.L.C. held a Generalitat Valenciana Pre-doctoral Fellowship. This work was supported by grants FIS 95/1672, DGES PM97-0082 and 1FD97-2297 (FEDER Programme) to J.M.J., the Spanish/British Joint Research Programme–Acciones Integradas/British Council (1997/98) to J.M.J. and W.W. (HB-3256), and Human Frontiers Science Program grant RG 17/98 to W.W.

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    Present address: Facultad de Medicina, Universidad de Castilla La Mancha, Campus de Albacete, 02071 Albacete, Spain.

    Present address: Università degli Studi di Roma “Tor Vergata”, Facoltà di Medicina e Chirurgia, Dipartimento di Neuroscienze, Rome, Italy.

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