Activation of the bilateral corticostriatal glutamatergic projection by infusion of GABA into thalamic motor nuclei in the cat: An in vivo release study

Abstract

The unilateral application of GABA (10 −5 M; 30 min) into thalamic motor nuclei of the cat increases the release of dopamine in both caudate nuclei. This effect has been suggested to be related to an activation of the bilateral corticostriatal glutamatergic projection, glutamate exerting a presynaptic facilitatory influence on dopamine release. To explore this hypothesis further, halothane-anesthetized cats implanted with push-pull cannulae were used in order to examine the effects of such a GABA application on the release of glutamate in both caudate nuclei. Aspartate, alanine, glutamine, serine and tyrosine were also measured in the superfusates. The unilateral application of GABA (10 −5 M; 30 min) into thalamic motor nuclei increased the release of glutamate bilaterally. Although less pronounced, ipsi- or bilateral increases in the efflux of alanine, glutamine and tyrosine were also observed. Contralateral changes in the efflux of glutamate, alanine and tyrosine were prevented following acute section of the corpus callosum. In addition, when applied continuously into one caudate nucleus, 2-amino-5-phosphonovaleric acid, a blocker of N-methyl- d-aspartate receptors, prevented the GABA-induced increase in alanine or tyrosine efflux but did not affect the enhanced release of glutamate. These results confirm that the unilateral application of GABA in thalamic motor nuclei activates a thalamo-cortico-striatal neuronal loop leading to the stimulation of glutamate release in both caudate nuclei. Changes in the efflux of other amino acids could be linked to increased metabolic activity of striatal target cells resulting from the increased release of glutamate and from its effect on N-methyl- d-aspartate receptors.