Abstract
The aim of the present study was to evaluate the expression of two high affinity GABA transporters (GAT-1 and GAT-3) in the rat cerebellum using immunocytochemistry and affinity purified antibodies. GAT-1 immunoreactivity was prominent in punctate structures and axons in all layers of the cerebellar cortex, and was especially prominent around the somata of Purkinje cells. In contrast, the deep cerebellar nuclei showed few if any GAT-1 immunoreactive puncta. Weak GAT-3 immunoreactive processes were present in the cerebellar cortex, whereas GAT-3 immunostaining was prominent around the somata of neurons in the deep cerebellar nuclei. Electron microscopic preparations of the cerebellar cortex demonstrated that GAT-1 immunoreactive axon terminals formed symmetric synapses with somata, axon initial segments and dendrites of Purkinje cells and the dendrites of granule cells. Astrocytic processes in the cerebellar cortex were also immunolabeled for GAT-1. However, Purkinje cell axon terminals that formed symmetric synapses with neurons in the deep cerebellar nuclei lacked GAT-1 immunoreactivity. Instead, weak GAT-1 and strong GAT-3 immunoreactivities were expressed by astrocytic processes that enveloped the Purkinje cell axon terminals. In addition, GAT-3-immunoreactivity appeared in astrocytic processes in the cerebellar cortex. These observations demonstrate that GAT-1 is localized to axon terminals of three of the four neuronal types that were previously established as being GABAergic, i.e. basket, stellate and Golgi cells. GAT-1 and GAT-3 are expressed by astrocytes. The failure to identify a GABA transporter in Purkinje cells is consistent with previous data that indicated that Purkinje cells lacked terminal uptake mechanisms for GABA. The individual glial envelopment of Purkinje cell axon terminals in the deep cerebellar nuclei and the dense immunostaining of GAT-3, and to a lesser extent GAT-1, expressed by astrocytic processes provide a compensatory mechanism for the removal of GABA from the synaptic cleft of synapses formed by Purkinje cell axon terminals.
Highlights
The Purkinje cells of the cerebellum are probably the first well-documented GABAergic inhibitory neurons in the mammalian brain (Eccles et al 1967; Chan-Palay 1977)
The results indicate that the axon terminals of three of the four GABAergic cerebellar neurons contain GAT-1 whereas those of the Purkinje cells lack GAD and 7-aminobutyric acid (GABA) transporters
One of the major findings of this study is that GAT-1, and not GAT-3, is found in the axon terminals of three GABAergic cell types in the cerebellum, but not in the fourth type, the Purkinje cells
Summary
The Purkinje cells of the cerebellum are probably the first well-documented GABAergic inhibitory neurons in the mammalian brain (Eccles et al 1967; Chan-Palay 1977). In the past 25 years, some doubt has been raised about Purkinje cells being GABAergic because they did not take up 3H-GABA when it was placed into the cerebellar cortex, deep cerebellar nuclei or vestibular nuclei (H6kfelt and Ljungdahl 1970; Kelly and Dick 1976; Tolbert and Bantli 1980; Wiklund et al 1983). 3H-GABA placed into the cerebellar cortex resulted in the labeling of basket, stellate and Golgi cells (H6kfelt and Ljungdahl 1970, 1972; Schon and Iversen 1972; Chan-Palay 1977; Tolbert and Bantli 1980). These studies indicated that Purkinje cells lack a GABA carrier that can take up GABA from the extracellular space
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