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R Romo

Publications and source records attributed to R Romo.

At least 55 records · Page 3Linked to original sources

Neuronal activity in the monkey striatum during the initiation of movements.

The sources of afferent input to the striatum (caudate nucleus and putamen) suggest that this structure may be engaged in neuronal processes related to the initiation of movement. We found that 26% of 508 neurons in both parts of the striatum were activated during the presentation of visual signals which prepared the animals for the execution or withholding of individual arm reaching movements. In a second task, 20% of 382 striatal neurons were activated up to 3 s before self-initiated, non automatic and purposive arm movements which were performed in the complete absence of phasic external stimuli. The data demonstrate an involvement of the striatum in externally and internally generated processes which are related to presetting mechanisms during the initiation of behavioral acts.

Action Potentials↗

Presynaptic regulation of dopaminergic transmission in the striatum.

1. 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. Recent in 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.

Animals↗

Different effects of electrical stimulation of the mesencephalic and pontine reticular formation on the release of dopamine and acetylcholine in the cat caudate nucleus.

The effects of unilateral electrical stimulation of the pontine (PRF) and mesencephalic (MRF) reticular formation on the release of acetylcholine (ACh) and of [3H]dopamine continuously synthesised from [3H]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 [3H]dopamine, whereas a significant reduction in [3H]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.

Acetylcholine↗

Neuronal activity preceding self-initiated or externally timed arm movements in area 6 of monkey cortex.

Several lines of evidence suggest that the supplementary motor area (SMA) and the premotor cortex (PM) may participate in neuronal mechanisms for the initiation of movements. We recorded the impulse activity of single neurons in monkeys that were trained in two behavioral tasks employing, respectively, self-initiated and externally timed movements. Neurons in both areas were activated up to 2.6 s in advance of self-initiated, reward-related arm reaching movements. In the externally timed task, changes occurred during light instructions that preceded movements by 2 s. Neurons also responded to the trigger stimulus for movement. In view of similar premovement activity in the basal ganglia, these cortical regions appear to be parts of a distributed neuronal system for movement initiation.

Animals↗

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.

Action Potentials↗

Responses of nigrostriatal dopamine neurons to high-intensity somatosensory stimulation in the anesthetized monkey.

Nigrostriatal dopamine (DA) neurons of the mammalian midbrain play an important role in behavioral reactions. Their destruction in Parkinsonian patients and experimentally lesioned animals leads to a reduction and slowing of movements as well as other motor, cognitive, and motivational deficits. We tested the responses of DA neurons to somatosensory stimulation to gain insight into the nature of peripheral information reaching these neurons. Experiments were performed as repeated sessions in two anesthetized monkeys having chronically implanted recording chambers, thereby reducing the number of primates required for experimentation. Midbrain DA neurons were characterized by their histological location, by the form, duration, and frequency of extracellularly recorded, spontaneously occurring impulses, by antidromic activation from caudate and putamen, and by the reduction of impulse rate following systemic administration of low doses of the DA autoreceptor agonist apomorphine. Half of the midbrain DA neurons (65 of 145 neurons, 45%) were antidromically activated from chronically implanted stimulating electrodes in caudate (35 neurons), putamen (47 neurons), or both structures (17 of them). Conduction velocities ranged from 0.7 to 2.5 m/s, with medians of 1.2 and 1.5 m/s for neurons projecting to caudate and putamen, respectively. Half of the midbrain DA neurons were depressed (72 of 140 neurons, 51%) and less than a quarter activated (24 of 140 neurons, 17%) by intense noxious pinch stimulation to the body surface. Innocuous, even intense, surface or deep somatosensory stimuli were ineffective. Pinch responses continued during the whole stimulating period of several seconds in most DA neurons. There was no response habituation during repeated stimulation. Convergence between spinal and trigeminal input and from both body sides was seen for virtually all noxious pinch responses. Thus DA neurons typically responded in the same direction to pinch stimulation of hand, foot, face, tail, and dorsum of both sides. Systemic administration of the DA receptor antagonist haloperidol (0.33 or 0.50 mg/kg) strongly reduced pinch responses in all seven DA neurons tested. This provides evidence for an involvement of DAergic neurotransmission in the representation of exteroceptive input in the brain. The results show that midbrain DA neurons projecting to the striatum respond to noxious somatosensory input in the anesthetized monkey. The bilateral nontopographic nature of the responses does not support a role in precise stimulus recognition, rather it suggests a mechanism involved in basic neuronal processes underlying behavioral responsiveness.

Anesthesia↗

Immunocytochemical study of enkephalin-like cell bodies in the thalamus of the cat.

Using an indirect immunoperoxidase technique, the localization of enkephalin-like cell bodies in the thalamus of the cat was carried out. Enkephalin-like cell bodies are widely distributed in the cat thalamus. However, immunoreactive cells may be regrouped in 4 clusters which do not exactly correlate with the anatomical subdivisions of the thalamus. One is located in the dorsocaudal aspect of the thalamus, another in the midline area, and the others are formed by the nuclei geniculatum mediale and laterale.

Animals↗

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.

Animals↗

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)

Animals↗

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

Animals↗

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)

Animals↗

Physiological presynaptic facilitation of dopamine release in the cat caudate nucleus.

Using halothane-anaesthetized cats implanted with push-pull cannulae, we investigated the effects of GABA application into the VM/VL on the release of [3H] DA continuously synthetized from [3H] tyrosine in the ipsilateral CN and SN and on single unit activity of nigral DA cells. GABA was applied (30 min) at a concentration of 10(-3) or 10(-5) M since the higher concentration reduces the local multi-unit activity in the VM/VL while the opposite response is observed with the lower one. The application of GABA into the VM/VL at a concentration of 10(-3) M resulted in an increase in nigral [3H] DA release, an inhibition of DA cell firing and a decrease in [3H] DA release in the CN. The latter effect is likely due to the inhibition of DA neuron activity which is triggered through DA autoreceptors by DA released from dendrites. In contrast, when applied at a concentration of 10(-5) M into the VM/VL, GABA stimulated [3H] DA release in the CN despite its inhibitory effect on single unit activity of DA cells. Furthermore, the nigral release of [3H] DA was no longer affected. These results indicated that DA release from nerve terminals was not dependent on nerve activity and they favour the existence of a potent facilitatory presynaptic regulation of DA release. The intervention of a presynaptic mechanism was further established by examining the effect of GABA (10(-5) M) application into the VM/VL on [3H] DA release in the CN shortly after a complete ipsilateral hemisection of the brain made at the meso-diencephalic level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prolonged changes in dopaminergic terminal excitability and short changes in dopaminergic neuron discharge rate after short peripheral stimulation in monkey.

Time-courses of responses to peripheral somatosensory stimulation were studied in the nigrostriatal dopamine (DA) system by comparing rates of neuronal discharges with changes in nerve terminal excitability, an indicator of DA release. The excitability of DA nerve terminals in the putamen was assessed as probability for evoking an antidromic response in substantia nigra DA cells with electrical stimulation in an anesthetized monkey. At about 30-60% decrease of excitability was seen during and about 15 min beyond pain pinch stimulation (PPS) in 12 of 17 tested DA neurons, while 4 neurons showed a 40% increase. Discharge rates were decreased in 7 and increased in 5 of the 17 DA neurons during, but not after PPS. It is concluded that the release of DA in the striatum may be controlled in two ways: rapid reactions would be mediated by changes in discharge rate, while slower, prolonged responses could be due to presynaptic interactions with other striatal afferents.

Action Potentials↗

Acetylcholine release in the cat caudate nucleus measured with the choline oxidase method.

A chemiluminescent assay for the estimation of acetylcholine (ACh) was used to measure ACh release in caudate nuclei (CN) of halothane-anaesthetized cats implanted with push-pull cannulae. The validity of the entire experimental approach used was shown by the fact that ACh release was calcium-dependent and was increased by depolarizing agents (potassium ions, veratridine) as well as by atropine. The effects of GABA (10(-5) M, 30 min) unilateral application into the ventralis medialis and ventralis lateralis thalamic nuclei on ACh release in both CN were then examined. This treatment, known to increase DA release bilaterally, decreased ACh release in both CN. These data further reveal the role of thalamic nuclei in the bilateral regulation of the activity of neurons identified within the basal ganglia and are discussed in the light of the well-known inhibitory influence of nigrostriatal DA neurons on striatal cholinergic neurons.

Acetylcholine↗

Role of thalamic motor nuclei in bilateral regulation of serotoninergic transmission in cat basal ganglia.

The effects of unilateral application of GABA (10(-5) M) into thalamic motor nuclei (ventralis medialis-ventralis lateralis, VM-VL) on 5-HT transmission in basal ganglia were investigated in halothane-anaesthetized cats implanted with several push-pull cannulae. The release of [3H]5-HT continuously synthesized from [3H]tryptophan was estimated in both caudate nuclei (CN), both substantia nigrae (SN) and in the dorsal raphe nucleus (DRN). [3H]5-HT release was decreased in the two CN and in the two SN but was enhanced in the DRN when GABA was applied into the VM-VL. These results indicate that thalamic motor nuclei are involved in a bilateral regulation of serotoninergic transmission in the basal ganglia.

Animals↗