ABSTRACT
Inactivation of amino acid neurotransmitters is generally held to be via high-affinity uptake into pre-synaptic neurones and glia, a model well established for monoaminergic systems. GABA for instance, is taken up at high affinity by glia and GABAergic neurones, and the two uptake systems have been distinguished by the use of competitive analogues in vivo and in vitro. Consequently, autoradiographic location of neuronal GABA uptake has become a useful method for recognition of GABAergic neurones. However, in the case of glutamate, the site(s) of high-affinity uptake are not well established and there are contradictions in the literature between results obtained by different methods. Biochemical studies on compartmentation in the metabolism of glutamate and the related amino acids GABA, aspartate and glutamine indicate strongly that glutamate uptake is exclusively located in glia. This is in accordance with the hypothesis of a neuronal-glial cycle in which glutamate passes from neurones to glia, and is returned to the neurones as glutamine. In vitro studies of uptake into isolated cell types show a high glial capacity for glutamate uptake. Studies of neuronal glutamate uptake in vitro are few and the results, although equivocal, indicate a lack of high-affinity uptake. Autoradiography of uptake of glutamate, or the non-metabolisable analogue, D-aspartate, has been performed in vivo by several groups of workers at the light and EM level. Some have reported only glial uptake, while others have reported a predominantly neuronal uptake of glutamate and have used this as a criterion for the presence of glutamatergic neurones. Considerable support for this interpretation comes from the finding that transection of the relevant pathways leads to a substantial reduction in the target tissue capacity for high-affinity glutamate uptake. Selective killing of supposed glutamatergic populations of neurones such as cerebellar granule neurones also leads to loss of glutamate uptake.
