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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 [ 3 H]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 [ 3 H]dopamine release was enhanced in the ipsilateral caudate nucleus and reduced in the contralateral structure while opposite responses were observed in the corresponcling substantiae nigrae. A reduction of [ 3 H]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 [ 3 H]dopamine release in the contralateral substantia nigra. No significant changes in [ 3 H]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.

Push-pull cannuale were implanted into the substantia nigra (SN) and the caudate nucleus (CN) of the cat to study the in vivo release of substance P (SP), using a radioimmunoassay and high pressure liquid chromatography (HPLC) analysis. The spontaneous release of SP could be detected in the SN and the CN. Potassium (50 mM) locally applied stimulated SP release in both structures. Furthermore an important evoked release of SP was observed in the SN during depolarization of striato-nigral SP fibers with potassium (50 mM) applied in the CN.

The effects of unilateral sensory stimuli on dopamine (DA) release from nerve terminals and dendrites of the two nigrostriatal dopaminergic pathways were estimated in halothane-anaesthetized cats without or with sagittal transections. In control animals, the electrical stimulation of the right forelimb enhanced DA release in the right caudate nucleus (CN) and decreased DA release in the right substantia nigra (SN). Opposite effects were observed in the contralateral structures. Sagittal transections of the corpus callosum and commissura anterior, or of the mesencephalic decussations or of the thalamic massa intermedia were made to investigate mechanisms involved in the reciprocal regulation of the two dopaminergic pathways. These sections were without effect on the spontaneous release of DA from nerve terminals and dendrites. The transection of the thalamic massa intermedia was the only one which interrupted the asymmetric changes in DA release induced by unilateral sensory stimuli; an increased dendritic release of DA was only seen in the left SN but it was significantly less pronounced than that observed in control cats. The other transections did not prevent the asymmetric changes in DA release evoked by the sensory stimulation. However, the mesencephalic sagittal transection significantly reduced the stimulatory effect on DA release induced in the left SN. These results suggest that the thalamus is involved in the transfer of information implicated in the reciprocal regulation of the two dopaminergic pathways. In the light of electrophysiological data, the role of nigrothalamic neurones in this phenomenon is discussed.

Acetylcholinesterase (AChE), which is known to inactivate acetylcholine (ACh), is present in great abundance in the substantia nigra, although ACh levels and choline acetylase activity in this region are relatively low1. Nigral dopaminergic cell bodies and their dendrites also contain AChE2–4. The functional significance of this enzyme in nigro-striatal dopaminergic neurones has been questioned1,4,5. Earlier studies demonstrated an evoked release of AChE from unidentified central neurones into cerebrospinal fluid (CSF) in cats6, rabbits7,8 and dogs9. Later experiments have provided indirect evidence that the substantia nigra may contribute to a substantial amount of AChE detected: a unilateral nigral lesion in rabbits reduced AChE levels in the CSF, whereas electrical stimulation of the substantia nigra induced the opposite effect10. To investigate the possible release of AChE from dopaminergic dendrites and terminals we measured the in vivo release of this enzyme from the substantiae nigrae and caudate nuclei of cats implanted with four push–pull cannulae and compared it with that of dopamine (DA). DA is released from dendrites in the substantia nigra11,12 as well as nerve terminals in the caudate nucleus. Spontaneous AChE release was observed in the substantia nigra and in the caudate nucleus. Moreover, the application of potassium (30 mM) in one substantia nigra increased the local release of AChE. This was accompanied by remote changes in the enzyme release from the other three structures which differed from that seen for DA. The different patterns of responses observed for AChE and DA suggest that AChE may also originate from other neurones in both the substantia nigra and the caudate nucleus.

USING cats implanted with push–pull cannulae, we have previously demonstrated a reciprocal regulation of the activity of the two nigro-striatal dopaminergic pathways. Asymmetric fluctuations in the spontaneous release of dopamine(DA) were simultaneously seen in the two caudate nuclei (CN)1. As revealed by the changes in DA release from nerve terminals, the unilateral nigral application of DA1 or of drugs enhancing the dendritic release of DA, such as amphetamine or benztropine (2), reduced the activity of ipsilateral dopaminergic neurones and induced an opposite effect in the contralateral side. Conversely, the unilateral nigral blockade of dopaminergic transmission by local application of neuroleptics enhanced the release of DA in the ipsilateral CN and decreased the transmitter release in the contralateral structure2. Opposite changes in the release of DA were also seen in the two CN under unilateral delivery of sensory stimuli3 or during unilateral electrical stimulation of the cerebellar dentate nucleus4. These latter effects were associated with asymmetric changes in the dendritic release of DA in the two substantia nigrae (SN) which were in an opposite direction to those seen in the two CN (an increased release of DA from nerve terminals corresponded to a decreased release of the transmitter from dendrites and vice versa). These experiments indicated that DA which is released from dendrites in one SN regulates the activity of the ipsilateral dopaminergic neurones; they also suggested that it contributes to the control of the contralateral dopaminergic neurones by influencing the dendritic release of DA in the contralateral SN. This hypothesis was confirmed in the present study by measuring the changes in DA release from nerve terminals and dendrites of the two pathways under pharmacological blockade or facilitation of dopaminergic transmission in one SN.

The release of [3H]DA synthesized from [3H]tyrosine was estimated in the two caudate nuclei (CN) during the unilateral nigral application of glycine and GABA-related compounds in 'encéphale isolé' cats using push-pull cannulae. Glycine (10(-5) M) reduced the release of [3H]DA in both CN and these effects were antagonized by strychnine (10(-5) M). A decrease in [3H]DA release was also seen in both CN during the unilateral nigral application of diazepam (10(-5) M). In contrast, muscimol (10(-6) M) and GABA (10(-5) M) stimulated [3H]DA release on both sides. The effect of GABA was blocked by picrotoxin (10(-5) M). Picrotoxin alone stimulated the release of [3H]DA in the ipsilateral CN and was without effect in the contralateral side. Bicuculline (10(-5) M) stimulated [3H]DA release only in the contralateral CN. A symmetric increase in [3H]DA release in both CN was also observed during the unilateral nigral application of potassium (30 mM). A model involving a facilitatory polysynaptic pathway originating from the substantia nigra (SN) and acting presynaptically on ther terminals of the contralateral DA neurons is proposed to explain the changes in [3H]DA release induced in the contralateral CN in these various situations. The results are discussed taking into account previous data on the reciprocal control of the two dopaminergic pathways induced by the unilateral nigral application of dopaminergic drugs.

Using push-pull cannulae, the release of newly synthesized 3H-DA was estimated in one substantia nigra (SN) and in the ipsilateral caudate nucleus (CN) of halothane anaesthetized cats. Applied into the SN, substance P (10−8M) reduced the dendritic release of 3H-DA but stimulated the release of the 3H-transmitter from nerve terminals in the CN. In contrast, a purified gamma-globulin fraction of a rabbit antiserum against substance P introduced into the SN reduced the release of 3H-DA from dendrites and induced an opposite effect in the CN. These results indicate that the striato-nigral substance P neurons exert an excitatory tonic influence on the nigrostriatal dopaminergic neurons. They are in agreement with the hypothesis of a critical role of the dendritic release of DA in the control of the activity of the dopaminergic neurons.

The effects of unilateral electrical stimulation of the pontine (PRF) and mesencephalic (MRF) reticular formation on the release of acetylcholine (ACh) and of [ 3 H]dopamine continuously synthesised from [ 3 H]tyrosine were examined in both caudate nuclei of halothane-anaesthetised cats implanted with push pull cannulae. Stimulation of PRF led to a prolonged bilateral increase in the release of [ 3 H]dopamine, whereas a significant reduction in [ 3 H]amine release was observed in the ipsilateral caudate nucleus following stimulation of the MRF. Changes in ACh release were also seen, but they seemed to be independent from those in dopamine release: the release of ACh was enhanced markedly in both caudate nuclei following stimulation of the MRF, whereas a more moderate increase in the release of ACh occurred ipsilaterally following stimulation of the PRF. These data indicate that both the MRF and the PRF are involved in the control of dopaminergic and cholinergic transmission in the basal ganglia.