R. Romo

In vivo presynaptic control of dopamine release in the cat caudate nucleus—II. Facilitatory or inhibitory influence ofl-glutamate

The local effects of various concentrations of L-glutamate (from 10(-8) M up to 10(-3) M) on the release of [3H]dopamine synthesized continuously from [3H]tyrosine were examined in the caudate nucleus of halothane-anaesthetized cats implanted with push-pull cannulae. When used at a concentration of 10(-8) M or 10(-7) M, L-glutamate stimulated the release of [3H]dopamine from nerve terminals of the nigrostriatal dopamine neurons. This effect was still observed in the presence of tetrodotoxin (5 X 10(-7) M) but it was antagonized by 2-amino 6-trifluoromethoxy benzothiazole (PK 26124) (10(-5) M), an antagonist dopamine nerve terminals. While no significant change in the release of [3H]dopamine was observed with 10(-6) M L-glutamate, higher concentrations (from 10(-5) M to 10(-3) M) of the amino acid produced a long-lasting reduction in the [3H]transmitter release. This latter effect was also antagonized by PK 26124 (10(-5) M) but, unlike that observed with 10(-8) M L-glutamate, it did not persist in the presence of tetrodotoxin (5 X 10(-7) M). On the contrary, a marked stimulation of the release of [3H]dopamine was seen in the presence of this neurotoxin. The reduction in the release of [3H]dopamine produced by 10(-4) M L-glutamate was also antagonized by bicuculline (10(-5) M) and moreover a marked stimulation of [3H]dopamine release took place in the presence of this gamma-aminobutyric acid (GABA) antagonist. Therefore, high concentrations of L-glutamate exerted an inhibitory presynaptic control on [3H]dopamine release which seemed to be indirect and mediated partly by GABAergic neurons. Since a sustained reduction in the spontaneous release of [3H]dopamine was seen in the presence of PK 26124, the corticostriatal glutamatergic neurons appeared to exert a tonic facilitatory presynaptic influence on dopamine release. This effect was important since it represented 40% of the tetrodotoxin-sensitive release of the [3H]transmitter. The direct (stimulatory) and indirect (inhibitory) presynaptic controls on dopamine release mediated by corticostriatal glutamatergic fibres are discussed in light of previous findings and of the anatomical organization of the caudate nucleus.

In vivo presynaptic control of dopamine release in the cat caudate nucleus—III. Further evidence for the implication of corticostriatal glutamatergic neurons

In confirmation of previous results, experiments in halothane-anaesthetized cats implanted with push-pull cannulae showed that the unilateral application of GABA (10(-5) M for 30 min) into the left thalamic motor nuclei (either ventralis medialis, or ventralis lateralis) markedly stimulated the release of [3H]dopamine continuously synthesized from [3H]tyrosine in both caudate nuclei and in the contralateral substantia nigra. Three types of experiments confirmed that the changes in [3H]dopamine release evoked in both caudate nuclei resulted from a presynaptic facilitation mediated by the bilateral corticostriatal glutamatergic projection: The constant delivery of 2-amino 6-trifluoromethoxy benzothiazole (PK 26124) (10(-5) M) to the left caudate nucleus prevented the increased release of [3H]DA evoked by application of gamma-aminobutyric acid (GABA) (10(-5)M) into ventralis medialis-ventralis lateralis while an enhanced release of [3H]dopamine still occurred in the contralateral caudate nucleus. Since PK 26124 is an antagonist of glutamatergic transmission, the presynaptic facilitation may involve glutamatergic neurons. Single unit recordings of dopamine cells in the contralateral substantia nigra indicated that the increased release of [3H]dopamine from dendrites evoked by the application of GABA (10(-5)M) into ventralis medialis-ventralis lateralis was associated with a reduction in the firing rate of dopamine cells. Thus, the enhanced release of [3H]dopamine in the contralateral caudate nucleus may involve a presynaptic facilitatory process. Finally, the unilateral lesion of the sensory motor cortex made prior to the superfusion of caudate nucleus with [3H]tyrosine prevented the responses evoked in the two caudate nuclei by the application of GABA (10(-4) M) into ventralis medialis-ventralis lateralis.(ABSTRACT TRUNCATED AT 250 WORDS)

Presynaptic regulation of dopaminergic transmission in the striatum

Summary1.In vitro studies have indicated that several transmitters present in the striatum can regulate presynaptically the release of dopamine (DA) from nerve terminals of the nigrostriatal DA neurons.2.The receptors involved in these local regulatory processes are located or not located on DA nerve terminals.3.Recentin vivo investigations have demonstrated that the corticostriatal glutamatergic neurons facilitate presynaptically the release of DA and have allowed the analysis of the respective roles of presynaptic events and nerve activity in the control of DA transmission.

Effects of unilateral electrical stimulation of various thalamic nuclei on the release of dopamine from dendrites and nerve terminals of neurons of the two nigrostriatal dopaminergic pathways

The role of several motor and intralaminar thalamic nuclei in the regulation of dopamine release from terminals and dendrites of the nigrostriatal dopaminergic neurons was investigated in halothane-anaesthetized cats. For this purpose, the effects of the unilateral electrical stimulation of various thalamic nuclei on the release of newly synthesized [3H]dopamine were simultaneously determined in both substantiae nigrae and caudate nuclei using the push-pull cannula method. The electrical stimulation of the motor nuclei was the only one to induce asymmetric changes in the four structures since [3H]dopamine release was enhanced in the ipsilateral caudate nucleus and reduced in the contralateral structure while opposite responses were observed in the corresponding substantiae nigrae. A reduction of [3H]dopamine release occurred in the four structures or only in the contralateral substantia nigra and caudate nucleus following the stimulation of the parafascicularis nucleus and the adjacent posterior part of the nucleus centrum medianum or of the nucleus centralis lateralis and the adjacent paralaminar part of the nucleus medialis dorsalis, respectively. The stimulation of the anterior part of the nucleus centrum medianum, which in contrast to other thalamic nuclei examined, receives few nigral inputs, selectively enhanced [3H]dopamine release in the contralateral substantia nigra. No significant changes in [3H]dopamine release were seen either in the substantiae nigrae or in the caudate nuclei following the stimulation of midline thalamic nuclei. These results indicate that the motor and intralaminar thalamic nuclei exert multiple and selective influences on the release of dopamine from terminals and/or dendrites of the dopaminergic neurons. They also further support a role of thalamic nuclei in the transfer of information from one substantia nigra to the contralateral dopaminergic neurons. The possible involvement of connections between paired thalamic nuclei was underlined by the observations of evoked potentials in contralateral homologous nuclei following unilateral stimulation of motor, or some intralaminar, nuclei. The present report provides new insights on the mechanisms contributing to the reciprocal and/or bilateral regulations of nigrostriatal dopaminergic pathways.

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.

Halothane-anaesthetized cats implanted with three push-pull cannulae were used to estimate the effects of gamma-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.(ABSTRACT TRUNCATED AT 400 WORDS)

Distinct commissural pathways are involved in the enhanced release of dopamine induced in the contralateral caudate nucleus and substantia nigra by unilateral application of GABA in the cat thalamic motor nuclei.

The effects of diencephalic or telencephalic commissural sectioning on the changes in [3H]dopamine ([3H]DA) release from nerve terminals (in the caudate nucleus, CN) and dendrites (in the substantia nigra, SN) of the two nigro-striatal dopaminergic pathways induced by the application of GABA (10(-5) M, 30 min) into the left ventralis medialis (VM) or ventralis lateralis (VL) thalamic nuclei were investigated. Experiments were performed in halothane-anesthetized cats implanted with push-pull cannulae in both CN and SN. In unlesioned cats, GABA application into the left VM-VL increased [3H]DA release in both CN and in the contralateral SN confirming previous results. Sectioning of the thalamic massa intermedia only blocked the GABA-induced increase in [3H]DA release in the contralateral SN, the responses in both CN being preserved. Sectioning of the rostral part of the corpus callosum only prevented the GABA-induced increase in [3H]DA release in the contralateral CN, whereas [3H]DA release in the ipsilateral CN and in the contralateral SN was still enhanced. These results suggest that changes in [3H]DA release evoked in both CN and in the contralateral SN by GABA application into the left VM-VL might involve different mechanisms: those observed in the CN result from potent pre-synaptic influences mediated by the bilateral cortico-striatal projections; those induced in the contralateral SN are due to other types of messages involving or passing through the thalamic massa intermedia.

GABA in the thalamic motor nuclei modulates dopamine release from the two dopaminergic nigrostriatal pathways in the cat

SummaryHalothane anesthetized cats were implanted with five push-pull cannulae and the release of (3H)dopamine (3H-DA), newly synthetized from (3H)tyrosine, was measured in both caudate nuclei (CN) and substantiae nigrae (SN). GABA was applied by means of one of the cannula in the ventralis medialis (VM) and the adjacent part of the ventralis lateralis (VL) nuclei of the thalamus. Autoradiographic studies performed with (14C)-GABA showed that the diffusion of the amino-acid in our experimental conditions was restricted to a 4.2 mm3 sphere at the tip of the push-pull cannula. Multi-unit activity was recorded both at the site of GABA injection and in the contralateral VM or VL nucleus. During and after a 30-min application of GABA (10−5M) in the VM-VL nuclei, neuronal firing was markedly enhanced locally and decreased in the homologous structures, while (3H)DA release increased in both CN and the contralateral SN. No effect was observed in the ipsilateral SN. These results show that thalamic motor nuclei could play a role in the regulation of the activity of the two dopaminergic nigrostriatal pathways and will be discussed in the light of previous data indicating a role of the thalamus in the bilateral regulation of dopaminergic transmission in the basal ganglia.

The role of dopamine released from distal and proximal dendrites of nigrostriatal dopaminergic neurons in the control of gaba transmission in the thalamic nucleus ventralis medialis in the cat

Halothane-anaesthetized cats implanted with push-pull cannulae were used in this study. Amphetamine was applied in the pars reticulata or pars compacta of the substantia nigra in order to determine the role of dopamine released from distal or proximal dendrites of dopaminergic cells in the control of GABAergic transmission in the nucleus ventralis medialis of the thalamus. When applied for 30 min in either the pars reticulata or the pars compacta, amphetamine (10(-6) M) enhanced to a similar extent the local release of [3H]dopamine synthesized from [3H]tyrosine, these effects being seen mainly during the drug application. The amphetamine-evoked release of dopamine in the pars reticulata produced a long lasting reduction in the release of [3H]GABA synthesized from [3H]glutamine in the nucleus ventralis medialis as well as in the paralamellar zone of the nucleus ventralis lateralis. Opposite effects were observed when amphetamine (10(-6) M) was applied in the pars compacta. In complementary experiments, single unit recordings were made in the intermediate part of the pars reticulata, some of the cells being identified by antidromic activation from the nucleus ventralis medialis. Whether applied in the pars reticulata or pars compacta, amphetamine (10(-6) M, 10 min) evoked a reversible decrease in the firing rate of most recorded cells whether or not they were identified as projecting to the nucleus ventralis medialis. Therefore, the decreased release of [3H]GABA in the nucleus ventralis medialis seen following application of amphetamine in the pars reticulata of the substantia nigra could result from an inhibition of nigrothalamic GABAergic neurons. Since the nucleus ventralis medialis is also innervated by GABAergic neurons originating in the entopeduncular nucleus, single unit recordings were made from cells in this nucleus during the application of amphetamine (10(-6) M, 10 min) into the pars compacta of the substantia nigra, some of which were identified antidromically as projecting to the nucleus ventralis medialis. Most cells identified or not were found to be activated during this treatment. These results suggested that the increased release of [3H]GABA seen in the nucleus ventralis medialis following application of amphetamine in the pars compacta of the substantia nigra might be linked to the enhanced firing rate of entopeduncular-thalamic GABAergic neurons.

Distribution of Met-enkephalin immunoreactive fibres in the thalamus of the cat.

The Met-enkephalin-like immunoreactivity was studied in the thalamus of the cat using an indirect immunoperoxidase method. The densest network of immunoreactive fibres and terminals was observed in the epithalamus and the intralaminar nuclei, particularly those located along the midline nuclei interanteromedialis, submedius, rhomboidens and reuniens. The nuclei parafascicularis and centrum medianum contained also numerous immunoreactive fibres and terminals, whereas the lamina medullaris externa had a lower density of immunoreactive terminals. Enkephalin fibres were almost totally absent in the lateral nuclei of the thalamus, and in the posterior group only the magnocellular part of the corpus geniculatum mediale contained some immunoreactive fibres.

Effects of electrical stimulation of various midline thalamic nuclei on the bilateral release of dopamine from dendrites and nerve terminals of neurons in the nigro-striatal dopaminergic pathways

The effects of electrical stimulation of midline thalamic nuclei on the release of [3H]dopamine ( [3H]DA) were determined in both substantiae nigrae (SN) and caudate nuclei of halothane-anesthetized cats using the push-pull cannula method. [3H]DA release was increased in the four structures following stimulation of the interanteromedialis nucleus (IAM) but only enhanced in both SN when nucleus reuniens (RE) was stimulated. In contrast, no effect was detected after delivery of the stimuli to nucleus centralis medialis. These results indicate that the anterior part of the thalamic massa intermedia (IAM and RE particularly) is involved in the bilateral regulation of DA release from nerve terminals and dendrites of the nigro-striatal dopaminergic neurons.