Developmental expression of γ-aminobutyric acid transporters (GAT-1 and GAT-3) in the rat cerebellum: evidence for a transient presence of GAT-1 in Purkinje cells

Abstract

The cerebellar cortex contains several classes of GABAergic neurons. Previous studies have shown that most GABAergic neurons in this region possess the capacity for γ-aminobutyric acid (GABA) uptake. The present study determined the postnatal expression of two GABA transporters, GAT-1 and GAT-3, in the cerebellar cortex and deep nuclei of the rat by using immunocytochemistry. Immunoreactivity for GAT-1 and GAT-3 appears at postnatal day 7 (P7), emerges centroperipherally across the cerebellum during the following 2 weeks and reaches an adult-like pattern by P30. The mature patterns are fully established by P45, which for GAT-1 is characterized by immunolabeled profiles localized exclusively to neuropil, mostly in the molecular layer and the pinceaux deep to the Purkinje cell bodies, and for GAT-3 as immunoreactivity distributed in the neuropil of mainly the granular layer. Before the adult patterns are completed, GAT-1 immunoreactivity is present in the somata of Purkinje, Golgi, basket and stellate cells between P7 and P21, while GAT-3 immunoreactivity is distinct in astrocytic somata which are organized in regularly spaced clusters. During this period, there is also a banding pattern in the sagittal plane of GAT-1 immunoreactivity in developing Purkinje cells. The postnatal development of GAT-1 and GAT-3 in the rat cerebellar cortex shares a similar spatiotemporal pattern with other GABAergic parameters, including the GABA synthesizing enzyme, GABA content and uptake. Specifically, the transient expression of GAT-1 in the somata and dendrites of cerebellar GABAergic neurons appears to correlate with the supra-adult levels of whole-tissue GABA uptake capability during development. Further, GAT-1 expression in immature Purkinje cells may play a unique role in regulating GABA's function during development, since mature Purkinje cells do not express GAT-1 or take up GABA.