Differential expression of GABA<sub>A</sub>/benzodiazepine receptor β<sub>1</sub>, β<sub>2</sub>, and β<sub>3</sub> subunit mRNAs in the developing mouse cerebellum

Journal of Comparative Neurology - Tập 326 Số 4 - Trang 580-594 - 1992
D Zdilar1, V Luntz-Leybman1, Adrienne Frostholm1, Andrej Rotter2
1Department of Pharmacology and the Neuroscience Program, The Ohio State University, Columbus, Ohio 43210
2Pharmacology and the Neuroscience Program, The Ohio State University, 333 West 10th Ave., Columbus, OH 43210

Tóm tắt

AbstractGamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian cerebellum. Cerebellar granule, Purkinje, and deep nuclear neurons are known to receive GABAergic afferents. Since GABA exerts its inhibitory effects via GABA receptors, it is of interest to determine the temporal relationship between the formation of GABAergic synapses and the expression of genes coding for the GABA receptor. In a previous study, we have examined the developmental expression of binding sites for [3H] muscimol, which binds with high affinity to the β subunits of the GABAA/benzodiazepine (GABAA/BZ) receptor. In the present study, [35S]cRNA probes were used to examine the appearance and distribution of GABAA/BZ β1, β2, and β3 subunit mRNAs in the developing C57BL/6 mouse cerebellum by in situ hybridization. In the adult cerebellum, the distribution of the three subunit mRNAs was clearly different, despite considerable overlap, and their temporal expression differed throughout postnatal development. The β1 hybridization signal appeared within the cerebellar cortex during the second postnatal week as a discrete band at the interface of the molecular and granule cell layers. Grains were distributed diffusely over small densely staining cells surrounding the Purkinje cells; relatively few grains were visible over Purkinje cell bodies themselves. This distribution may reflect an association with Bergmann glia or basket cells. The β2 and β3 hybridization signals were present considerably earlier than that of the β1 mRNA. The β2 signal was present at birth in the molecular/Purkinje cell layer; as development progressed, the signal became increasingly intense over both granule and Purkinje cells. At birth, the β3 subunit mRNA was present in the external germinal and molecular layers, later becoming largely localized within the granule cell layer. Dense β2 and β3 cRNA probe labeling was present over the adult granule cell layer. Moderate levels of β2 signal were seen over Purkinje cell bodies; considerably less labeling was observed with the β3 probe. The adult distribution of β2 and β3 cRNA probes showed good spatial correspondence with the known GABAA receptor β subunit markers, [3H]‐muscimol and the mAb 62‐3G1 antibody, each being present within the granule cell layer.Our results indicate that the temporal expression of GABAA/BZ receptor β subunit messages within a given cell type may be independently regulated, and that acquisition of the β2 and β3 mRNAs occurs before these cells become integrated into mature synaptic circuits. © 1992 Wiley‐Liss, Inc.

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Journal of Comparative Neurology

Tập 326 Số 4

580-594

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