The ontogeny of [ 3H]muscimol binding sites in the C57BL/6J mouse cerebellum

Abstract

The characteristics of [ 3H]muscimol binding were investigated in cerebellar sections from 7-day-old mice. The binding sites were found to possess the kinetic properties and pharmacological specificity characteristic of high-affinity GABA A receptors. [ 3H]Muscimol binding sites in the developing C57BL/6J mouse cerebellum were visualized by light microscopic autoradiography. A distinct band of labeling situated over the molecular layer was apparent from day 1 to day 7. The external granule cell layer remained unlabeled throughout development. Labeling over the internal granule cell layer gradually increased from birth; it became more dense and well defined until adult levels of grain density were reached at 35–42 days of age. The deep cerebellar nuclei were moderately labeled at birth and gradually decreased in density thereafter. The observed ontogeny of granule cell [ 3H]muscimol binding sites suggests that the synthesis of receptors is initiated at a time immediately after cessation of cell division, coinciding with the beginning of granule cell translocation across the molecular layer. Since, at this time, granule cells have not yet formed synapses with the GABAergic Golgi II cells, nor have they, in turn, formed the vast majority of synaptic contacts with Purkinje cells, it follows that receptor appearance precedes the formation of afferent connections, and may also precede efferent synaptic contacts. The timing of the appearance of [ 3H]muscimol binding sites raises the possibility that their initial acquisition may be related to developmental events other than the interaction of the granule cell with its pre- or postsynaptic neuronal partners.