High affinity uptake of glutamate in terminals of corticostriatal axons

Abstract

GLUTAMIC ACID (glu) may be the transmitter of a large proportion of excitatory synapses in the brain¹, but glu is also important in cell metabolism, and the apparent lack of biochemical ‘markers’ associated with the role of glu as a synaptic transmitter has until recently hampered the localisation of potential ‘glutamergic’ neurones. High affinity uptake of glu^2,3 is, however, highly specific² and seems to be selectively localised in the excitatory granular cell terminals in the cerebellum⁴, and in three systems of excitatory nerve endings in the hippocampal formation, as shown by autoradiography⁵ and quantitative measurements⁶. In the conditions used in these studies, glial uptake of glu^7,8 was found not to be quantitatively important. In the hippocampal systems, iontophoretic studies⁹ and release experiments¹⁰ strongly suggest that glu, and/or aspartic acid (asp), may be the transmitter. It thus seems that high affinity uptake of glu may be useful as a marker for putative glutamergic and/or aspartergic nerve endings. The question of whether the uptake of [³H]glu, as measured in vitro, represents net accumulation or homoexchange¹¹ is not crucial in the present context. The neostriatum (nucleus caudatus–putamen) receives a large excitatory projection from the neocortex^12,13. Iontophoretic studies suggest that this could use glu or asp as its transmitter^1,14. We here demonstrate that high affinity uptake of glu is selectively reduced in the neostriatum after lesions in the neocortex.