Transient expression of GABA A receptor α2 and α3 subunits in differentiating cerebellar neurons

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In the adult mammalian brain, synaptic transmission mediated by γ-amino butyric acid (GABA) plays a role in inhibition of excitatory synaptic transmission. During brain development, GABA is involved in brain morphogenesis. To clarify how GABA exerts its effect on immature neurons, we examined the expression of the GABA A receptor α2 and α3 subunits, which are abundantly expressed before α1 and α6 subunits appear, in the developing mouse cerebellum using in situ hybridization. Proliferating neuronal precursors in the ventricular zone and external granular layer expressed neither α2 nor α3 subunits. Hybridization signals for the α2 and α3 subunit mRNAs first appeared in the differentiating zone at embryonic day 13 (E13). The α2 subunit was detected in the migrating and differentiating granule cells and cerebellar nucleus neurons until postnatal day 14 (P14). Hybridization signals for the α3 subunit mRNA, on the other hand, were localized in the developing Purkinje cells and cerebellar nucleus neurons, and disappeared from Purkinje cells by the end of first postnatal week. Taken together, this indicated that the α2 and α3 subunits were abundantly expressed in distinct types of cerebellar neurons after completing cell proliferation while forming the neural network. These results suggest that GABA might extrasynaptically activate the GABA A receptors containing α2 and/or α3 subunits on the differentiating neurons before finishing the formation of synapses and networks, and could be involved in neuronal differentiation and maturation in the cerebellum.