Ce. Ribak et al., ASTROCYTIC PROCESSES COMPENSATE FOR THE APPARENT LACK OF GABA TRANSPORTERS IN THE AXON TERMINALS OF CEREBELLAR PURKINJE-CELLS, Anatomy and embryology, 194(4), 1996, pp. 379-390
The aim of the present study was to evaluate the expression of two hig
h affinity GABA transporters (GAT-1 and GAT-3) in the rat cerebellum u
sing immunocytochemistry and affinity purified antibodies. GAT-1 immun
oreactivity was prominent in punctate structures and axons in all laye
rs of the cerebellar cortex, and was especially prominent around the s
omata of Purkinje cells. In contrast, the deep cerebellar nuclei showe
d few if any GAT-1 immunoreactive puncta. Weak GAT-3 immunoreactive pr
ocesses were present in the cerebellar cortex, whereas GAT-3 immunosta
ining was prominent around the somata of neurons in the deep cerebella
r nuclei. Electron microscopic preparations of the cerebellar cortex d
emonstrated 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 th
e 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 additio
n, GAT-3-immunoreactivity appeared in astrocytic processes in the cere
bellar cortex. These observations demonstrate that GAT-1 is localized
to axon terminals of three of the four neuronal types that were previo
usly established as being GABAergic, i.e. basket, stellate and Golgi c
ells. GAT-1 and GAT-3 are expressed by astrocytes. The failure to iden
tify a GABA transporter in Purkinje cells is consistent with previous
data that indicated that Purkinje cells lacked terminal uptake mechani
sms for GABA. The individual glial envelopment of Purkinje cell axon t
erminals in the deep cerebellar nuclei and the dense immunostaining of
GAT-3, and to a lesser extent GAT-1, expressed by astrocytic processe
s provide a compensatory mechanism for the removal of GABA from the sy
naptic cleft of synapses formed by Purkinje cell axon terminals.