In vivo presynaptic control of dopamine release in the cat caudate nucleus—I. Opposite changes in neuronal activity and release evoked from thalamic motor nuclei

Abstract

Halothane-anaesthetized cats implanted with three push pull cannulae were used to estimate the effects of γ-aminobutyric acid (GABA) application (either 10 −3 M or 10 −5 M ) into the left motor nuclei of the thalamus (either ventralis medialis, or ventralis lateralis) on the firing rate of dopamine cells in the left substantia nigra (caudomedial part) and on the release of [ 3H]dopamine continuously synthesized from [ 3H]tyrosine, in the left substantia nigra (caudomedial part) and the left caudate nucleus. Preliminary experiments were performed to establish the electrophysiological characteristics of dopamine cells and non-dopamine cells in the pars compacta (mediocaudal part of substantia nigra) in groups of animals with the electrode inserted within the nigral push pull cannula or with the electrode inserted in the absence of a push-pull cannula. Dopamine and non-dopamine cells were distinguished according to several criteria (shape of the spike, duration of spike, frequency of discharge, conduction velocity estimated following antidromic activation from the caudate nucleus for dopamine cells or from the ventralis medialis for non-dopamine cells). Data obtained from recordings made within the push pull cannula were identical to those obtained in the absence of the cannula. In addition both the intravenous injection of amphetamine or its local application (10 −6 M) in the substantia nigra inhibited the firing rate of dopamine cells. When GABA was applied at 10 −3 M for 30 min into the ventralis medialis ventralis lateralis the multi-unit activity of thalamic cells recorded within the push pull cannula was inhibited. Single unit activity of dopamine cells was also inhibited and [ 3H]dopamine release was reduced in the caudate nucleus and increased in the substantia nigra. These results suggest that under these conditions, dopamine release from nerve terminals depended upon nerve activity and that dopamine released from dendrites inhibited the activity of dopamine cells. When GABA was applied at 10 −5 M for 30 min into the ventralis medialis-ventralis lateralis, multi-unit activity of thalamic cells was increased, single-unit activity of dopamine cells was inhibited and [ 3H]dopamine release was enhanced in the ipsilateral caudate nucleus and not affected in the left substantia nigra, demonstrating that in this situation the release of dopamine from nerve terminals was not dependent on the firing rate of dopamine cells. In addition, these results indicated that the activity of dopamine cells was not always dependent on the dendritic release of dopamine. Further experiments performed in cats with an acute hemi-transection (left side) made just in front of the substantia nigra to cut through all dopamine fibres confirmed that the GABA (10 −5 M )-evoked release of [ 3H]dopamine in the caudate nucleus was mediated by a presynaptic regulation triggered from thalamic-motor nuclei. Indeed, [ 3H]dopamine release was still enhanced by GABA (10 −3 M) application into the ventralis medialis-ventralis lateralis of such animals. In contrast the application of GABA (10 −3 M) into the ventralis medialis-ventralis lateralis was without effect on [ 3H]dopamine release; n the caudate nucleus of the hemi-transected animals. Results are discussed in the light of the respective contributions of nerve activity and presynaptic regulation in the control of dopamine transmission in the caudate nucleus.