Activity Of Pallidal Neurons Research Articles

Excitotoxic acid lesions of the primate subthalamic nucleus result in reduced pallidal neuronal activity during active holding.

1. To gain a better understanding of the pathophysiology of hemiballismus in primates, and to test directly the hypothesis that the subthalamopallidal projection is excitatory, we studied the effects of lesions of the subthalamic nucleus (STN) on neuronal activity in the globus pallidus (GP) of monkeys during performance of a motor behavioral task. 2. Animals were trained to position and hold a manipulandum to which torque pulses were applied, producing elbow flexion and extension. The activity of neurons in the external (GPe) and internal (GPi) segments of GP was recorded in two monkeys during task performance before and after STN lesions. The STN was lesioned by the fiber-sparing neurotoxins ibotenic acid and/or kainic acid. 3. After lesioning, the firing rate of neurons in both segments of GP, which was measured during the period of holding before torque application, was significantly decreased in both animals. The mean of discharge rates of GPi neurons decreased (P < 0.001) from 69.8 (n = 169, SD = 21.6) to 47.4 spikes/s (n = 180, SD = 22.6) after lesioning. The mean of discharge rates of GPe neurons decreased from 63.6 spikes/s (n = 218, SD = 25.1) before lesions to 41.0 spikes/s (n = 208, SD = 18.1) after lesioning. 4. These results provide further evidence that STN gives rise to a major excitatory input to both segments of the GP and support the hypothesis that dyskinesias result from decreased GPi output.

Apomorphine-induced changes in striatal and pallidal neuronal activity are modified by NMDA and muscarinic receptor blockade

Systemic administration of apomorphine decreased the firing rate of caudate Type I neurons and increased the firing rate, presumably via disinhibition (16), of globus pallidus (GP) Type II neurons. In the present study, extracellular single-unit recording techniques were used to demonstrate that systemic administration of the NMDA antagonist dizocilpine (MK801) reduced both the inhibition of caudate neurons by apomorphine as well as the apomorphine-induced excitation of GP neurons. In addition, the muscarinic antagonists atropine and scopolamine had effects similar to dizocilpine. Thus, both glutamate and acetylcholine appear to play a role in dopaminergic modulation of striatal and GP activity.

Effects of dopamine agonists on the spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism

The mixed (D 1 and D 2) dopamine agonist apomorphine was injected (10–200 μg/kg, s.c.) to cynomolgus monkeys before and after they were rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Motor behavior was examined together with corresponding neuronal activity in the external (GPe) and internal (GPi) segments of the globus pallidus, including a small population of neurons localized within the GPe and displaying a characteristics discharge at low frequency with bursts (LFB), and border (Bor) neurons localized at the periphery of the pallidal segments. In the intact animal strong but not weak doses of the drug induced generalized agitation without apparent neuronal effects. In 1 parkinsonian animal that showed some recuperation of normal behavioral and pallidal activity, weak doses induced agitation and partly reduced the signs of parkinsonism, again without apparent neuronal effects. The same results were obtained before day 21 after MPTP in a parkinsonian monkey that did not recuperate. After day 21, however, the drug acted at a shorter latency, completely abolished the signs of parkinsonism, induced dyskinesia, increasing with repetition of injections, and clear neuronal effects. The same results were obtained from the start in another monkey in which recordings were begun 398 days after MPTP. Nearly all GPi neurons decreased their firing rate following apomorphine. The reverse was true of the predominant neuronal population in the GPe. In both cases, the intensity of the changes in firing rate varied much between neurons following the same dose of apomorphine. When the changes in firing rate were moderate or null, abnormal bursting firing patterns were normalized. Both LFB and Bor neurons decreased their firing rate following apomorphine; LFB neurons being extremely sensitive. The selective D 2 agonist RU-24213 induced behavioral and neuronal effects identical to those of apomorphine.

Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism

The goal of the study was to determine abnormalities in the spontaneous activity of globus pallidus at the output of the basal ganglia, in cynomolgus monkeys rendered parkinsonian by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In parkinsonian compared to intact monkeys, the mean spontaneous firing rate of the neurons of the internal segment of the globus pallidus (GPi) increased but that of the prevailing neuronal population in the external segment (GPe) inversely decreased. Correspondingly, the mean modal interval between spikes shortened, suggesting increased excitation, in both the GPi and GPe. However, the mean proportion of intervals longer than 100 ms increased in the GPe but remained unchanged in the GPi, suggesting increased inhibition only in the GPe. In the two populations, bursting activities and the mean variability of firing rate increased. Concurrently, a small and distinct neuronal population located in the GPe and another located at the periphery of both the GPi and GPe displayed minor changes, which were however different from those observed in the GPi and in the prevailing neuronal population of the GPe. The intensity of changes varied with time and severity of nigral lesion. In severe parkinsonism, the neuronal activity at the output of the basal ganglia (GPi) is excessive.

Nigrostriatal lesion alters neurophysiological responses to selective and nonselective D‐1 and D‐2 dopamine agonists in rat globus pallidus

The effects of the selective D-1 dopamine agonist SKF 38393, the selective D-2 agonist quinpirole, and the nonselective D-1/D-2 agonist apomorphine on spontaneous activity of globus pallidus neurons were compared in normal control rats and rats with unilateral 6-hydroxydopamine induced lesions of the nigrostriatal pathway. In control, unlesioned rats, SKF 38393 (0.4 and 10 mg/kg, i.v.) caused no significant net change in the activity of globus pallidus neurons, although some individual cells showed significant increases or decreases in discharge rates following 10 mg/kg SKF 38393 administration. In animals with unilateral 6-hydroxydopamine induced lesions, SKF 38393 caused greater increases and decreases in the discharge rates of a larger percentage of pallidal cells recorded on the ipsilateral side than in control, unlesioned animals. These rate changes were effectively reversed by the D-1 antagonist SCH 23390, but not by the D-2 antagonist YM-09151-2. Quinpirole (0.3 mg/kg, i.v.) produced modest rate increases in control, unlesioned animals and significantly larger rate increases in nigrostriatal lesioned animals. YM-09151-2, but not SCH 23390, effectively reversed quinpirole's effects in the lesioned animals. As previously reported, the nonselective D-1/D-2 agonist apomorphine (0.3 mg/kg, i.v.) produced large increases in discharge rates of pallidal cells in control, unlesioned rats. In contrast, in nigrostriatal lesioned rats, the discharge rates of some ipsilateral pallidal neurons were markedly increased, others were decreased, and some were unaffected following apomorphine administration. The dopamine antagonist spiroperidol partially to fully reversed these rate changes. In summary, apomorphine's neurophysiological profile appears to be an exaggeration of the D-1 agonist profile in the globus pallidus of these lesioned animals. The degree of change observed after apomorphine administration is consistent with results from other studies that have indicated that a synergistic interaction between effects triggered by stimulation of the two receptor subtypes can occur in these animals, as in control, unlesioned animals. However, these results further show that in rats with unilateral nigrostriatal lesions, the denervated dopamine receptors or the processes they mediate are altered so that they no longer have the requirement seen in controls for concurrent stimulation of the complementary dopamine receptor subtype for expression of the selective agonist effects.

The effects of striatal lesion on turning behavior and globus pallidus single unit response to dopamine agonist administration

In normal rats, globus pallidus neurons are excited by the systemic administration of postsynaptically active doses of apomorphine. The role of the striatum in mediating this phenomenon was examined by investigating the effects of apomorphine on neuronal activity in the globus pallidus and on turning behavior in rats with unilateral quinolinic acid lesions of the striatum. The lesion markedly reduced striatal choline acetyltransferase activity and GABA content and significantly attenuated apomorphine's effect on the activity of pallidal neurons. Both the extent of attenuation of the electrophysiological response of pallidal neurons in lesioned animals and the neurotoxin-induced decreases in choline acetyltransferase activity and GABA content in the caudal striatum were correlated with the degree of apomorphine-induced turning. The data indicate that striatopallidal neurons contribute to apomorphine's excitatory effect on the activity of pallidal neurons in normal animals.

Acute reduction of dopamine levels alters responses of basal ganglia neurons to selective D-1 and D-2 dopamine receptor stimulation

Extracellular single unit recording techniques were used to investigate dopamine agonist-induced changes in the tonic activity of globus pallidus neurons in normal control rats, and in rats in which dopamine levels were acutely reduced by α-methyl-para-tyrosine (AMPT) pretreatment. Systemic administration of the nonselective D-1/D-2 agonist apomorphine consistently induced large increases in the firing rates of globus pallidus neurons, as shown previously. The D-1 agonist SKF 38393 frequently induced no change in pallidal cell firing rates with doses up to 20 mg/kg; however, firing rates of 40% of the cells were stimulated by more than 20% of baseline and 14% were partially inhibited after 20 mg/kg SKF 38393. Following AMPT pretreatment, SKF 38393 induced only increases and no changes in activity; no decreases were observed. The D-2 agonist quinpirole typically increased pallidal neuron activity in a dose-dependent manner but was markedly less effective at stimulating pallidal neuron activity than apomorphine. In AMPT-treated rats, quinpirole's effects were significantly attenuated. Consistent with previous results, most cells showed large rate increases when SKF 38393 and quinpirole were coadministered to normal rats; these increases were similar in magnitude to those induced by apomorphine. In contrast to the observation that AMPT treatment altered the responses of globus pallidus neurons to individually administered quinpirole and SKF 38393, neither the increases in pallidal cell activity induced by apomorphine nor those induced by coadministration of SKF 38393 and quinpirole were significantly attenuated in AMPT-treated rats. The results support the idea that stimulation of both D-1 and D-2 receptors appears to be required to induce apomorphine-like changes in basal ganglia output. Moreover, the effects of individually administered D-1 and D-2 agonists observed in normal rats appear to depend upon the degree to which the complementary receptor subtype is stimulated by endogenous dopamine.

Abnormal influences of passive limb movement on the activity of globus pallidus neurons in parkinsonian monkeys

Extracellular single unit activity was recorded in the globus pallidus of waking Macaca fascicularis during passive limb movement. The main upper and lower limb joints were investigated bilaterally. The animals were either intact or rendered parkinsonian by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell counts showed that at least 90% of nigral neurons of the compacta-type were degenerated in the parkinsonian animals. In the intact animals, only 17% of the pallidal neurons responded to the natural stimulus. As already reported by others, the responses were typically related to movement about a single contralateral joint and in only one direction. In the parkinsonian animals, however, more neurons responded, often more vigorously, to the same stimulation. In many of these neurons the responses were elicited by movement about more than one joint of both upper and lower limbs or ipsi-and contralateral sides and in more than one direction. The increase in number and magnitude and loss of specificity of responses were much greater in the internal pallidal segment, where the number of responding neurons quadrupled. These results suggest that dopaminergic mechanisms regulate gain and selectivity in the basal ganglia. In animals with decreased dopaminergic functions, the excessive and unselective motor responses may explain all 3 major signs of parkinsonism: rigidity, tremor and akinesia.

Chorea and myoclonus in the monkey induced by gamma-aminobutyric acid antagonism in the lentiform complex. The site of drug action and a hypothesis for the neural mechanisms of chorea.

Experiments are described in which the gamma-aminobutyric acid (GABA) antagonist bicuculline was injected into the lentiform complex of conscious monkeys. Injections into either the lateral segment of the globus pallidus, or the medial part of the putamen, gave rise to chorea of the contralateral limbs and/or orofacial region. Control injections of vehicle alone were without effect. Injections of bicuculline into the lateral part of the putamen gave rise to contralateral myoclonus. The chorea produced by lateral pallidal or medial putaminal injections was virtually indistinguishable from the dyskinesia (chorea/ballism) which has been shown, in previous studies, to be induced by injection of GABA antagonists into the subthalamic nucleus. It is proposed that the primary site of action of the GABA antagonist in producing chorea, in the present studies, was the lateral segment of the globus pallidus. The mode of action is suggested to be interruption of GABAergic transmission from the striatum to the lateral pallidal segment. Since this also occurs in Huntington's disease, it is proposed that experimental chorea induced by this method in the monkey may be a useful model of the dyskinesia seen in Huntington's disease in man. Loss of influence of inhibitory striatopallidal fibres would lead to abnormally increased activity of lateral pallidal neurons. These in turn project to the subthalamic nucleus, upon which they have an inhibitory action. Dyskinesia is thus produced by physiological inhibition of the subthalamic nucleus, whose destruction, both in man and the monkey, is known to produce ballism. It is proposed that ballism and chorea share common neural mechanisms, both involving the loss of influence of the subthalamic nucleus on the medial segment of the globus pallidus.

Stimulation of both D 1 and D 2 dopamine receptors appears necessary for full expression of postsynaptic effects of dopamine agonists: a neurophysiological study

The abilities of 4 dopamine agonists to inhibit the tonic single unit activity of substantia nigra dopamine neurons and stimulate tonic activity of globus pallidus neurons were compared to study the agonists' effects on pre- and postsynaptic dopamine receptors, respectively. The agonists studied were apomorphine and pergolide, which interact with both D 1 and D 2 receptors, and the selective D 2 agonists quinpirole and RU 24926. Drugs were administered systematically. The 4 dopamine agonists were equipotent and equiefficacious at inhibiting the firing rates of dopamine neurons. In contrast, their effects on pallidal cells were not identical; apomorphine and pergolide induced significantly greater increases in pallidal cell activity than did quinpirole and RU 24926. In addition, pretreatment with a small dose of quinpirole did not attenuate the excitatory effect of apomorphine on globus pallidus cell activity, as low doses of apomorphine have previously been shown to do. Possible mechanisms underlying the differences in efficacy between the non-selective and D 2 selective dopamine agonists in the globus pallidus were investigated. Coadministering quinpirole with apomorphine did not significantly attenuate the effect of apomorphine, suggesting that quinpirole is not a partial agonist at postsynaptic dopamine receptors. In addition, prazosin pretreatment did not attenuate the stimulatory effect of pergolide on firing rates of pallidal cells, indicating that the greater efficacy of the non-selective agonists was not due to concurrent stimulation of α 1 adrenergic receptors and dopamine receptors. However, the effect of quinpirole on pallidal cell activity was significantly potentiated by pretreatment with the D 1 agonist RS-SKF 38393 but not its inactive enantiomer S-SKF 38393. These results suggest that concurrent D 1 and D 2 receptor stimulation may be necessary for the full expression of postsynaptic receptor-mediated effects of dopamine and dopamine agonists in the basal ganglia.

Influence of the globus pallidus on arm movements in monkeys. III. Timing of movement-related information.

Monkeys were trained to make a visually triggered arm-reaching movement to a lighted button in a simple reaction-time paradigm, during which the reaction time (RT) and movement time (MT) were measured. Stimulus trains of varying duration were applied at various times before and during the movement at locations in the globus pallidus where application of long stimulus trains caused increased MTs. A critical stimulus period was identified during which stimulus application effectively prolonged MTs. The activity of pallidal neurons was examined during performance of the same behavioral task. More than 60% of the neurons examined showed task-related changes in activity that began before or during the reaching movement. For 45% of these cells, the initial change in firing occurred during the critical stimulus period, 50-150 ms before mechanically detected movement. Comparison of the critical stimulus period, the time of task-related changes in the discharge of pallidal neurons, and the time of EMG activity in muscles acting at the back, shoulder, elbow, and wrist revealed that both the critical stimulus period and changes in neuronal discharge occurred at or after initial muscle activation and during the buildup of EMG activity. These data are consistent with a model in which the globus pallidus plays a role in scaling the magnitude of muscle activity that determines movement velocity without affecting the initiation or sequential organization of the programmed motor output.

Effects of enkephalin and morphine on rat globus pallidus neurons

This study was conducted in order to compare the effects of microiontophoretically-applied morphine and met-enkephalin (met-ENK) on spontaneous and/or glutamate-evoked activity of single globus pallidus (GP) neurons in locally anesthetized, paralyzed rats. The predominant effect of both morphine and met-ENK was a depression of pallidal neuronal activity. While very few GP neurons were excited by morphine ( 2 89 ), a small population of neurons was excited by met-ENK ( 16 89 ). Both the inhibitory and excitatory responses produced by morphine and met-ENK could be attenuated by the microiontophoretic application of naloxone. It was also found that morphine and met-ENK did not affect all GP neurons in a similar manner. When applied to the same neurons, morphine elicited depression in 11 of 16 GP neurons which were excited by the application of met-ENK. In contrast, neither of two GP neurons excited by morphine in this study displayed inhibition upon application of met-ENK. Thus the microiontophoresis of morphine and met-ENK to single GP neurons has demonstrated that these two substances can produce opposite effects when applied to the same neurons and suggests that two functionally distinct types of opiate receptor may exist within rat GP, one which mediates the inhibitory effects of morphine and met-ENK, possibly the classical mu (μ) receptor, and one that is preferentially selective to met-ENK and which mediates the excitatory effects of opiates within this region, possibly the classical delta (δ) receptor.

Dopamine attenuates the effects of GABA on single unit activity in the Globus pallidus

Studies were conducted to assess whether stimulation of dopamine receptors located in the globus pallidus might play a role in mediating the enhanced pallidal activity seen after systemic administration of dopamine agonists or d-amphetamine. Dopamine, applied iontophoretically, had modest effects on the activity of pallidal neurons; the baseline firing rates of 32% of cells recorded increased by an average of23 ± 2%, 18% decreased in rate and the remaining cells showed no significant rate change. More significantly, dopamine consistently attenuated the inhibitory actions of gamma-aminobutyric acid (GABA) in the globus pallidus. When dopamine was simultaneously iontophoresed with GABA, GABA's effectiveness at inhibiting pallidal activity was reduced by an average of 50%. Norepinephrine or acetylcholine, applied iontophoretically at equimolar concentrations and ejected at the same current as dopamine, caused no consistent attenuation of pallidal responses to GABA's rate effects. To determine whether the attenuation of GABA's inhibitory action by iontophoresed dopamine could be mimicked by systemic drug administration, apomorphine, 80 μ/kg, or d-amphetamine, 0.8 mg/kg, was given i.v. while GABA was iontophorosed. Apomorphine markedly decreased pallidal responses to the inhibitory effects of GABA in 75% of the cells by an average of 50%; haloperidol reversed this effect. Modulatory interactions between GABA and d-amphetamine were also observed in 5 of the 11 pallidal cells tested; GABA's inhibitory effect on pallidal cell activity was reduced by an average of 66% on these neurons. These results suggest that one way in which dopamine and dopamine agonists may effect basal ganglia function is by modulating GABAergic transmission in the globus pallidus.

Dopamine agonists increase pallidal unit activity: Attenuation by agonist pretreatment and anesthesia

Intravenous administration of a single bolus dose of 1 μ mol/kg of the dopamine agonists, pergolide and lisuride, caused marked increases in the unit activity of globus pallidus neurons in awake, paralyzed, locally anesthesized and artificially respired rats. These agonist effects were similar to those observed after administration of 1 μ mol/kg apomorphine to awake, paralyzed rats; in rats anesthetized with chloral hydrate, however, responses to apomorphine were markedly attenuated. Subsequent administration of haloperidol reversed the effects of pergolide and pretreatment with haloperidol blocked the effects of lisuride. LSD (1 μ mol/kg i.v.) did not effectively stimulate pallidal neuronal activity, suggesting that the ability to stimulate pallidal firing rates correlates better with dopamine, as opposed to serotonin, agonist potency. The ability of a non-excitatory dose of apomorphine to attenuate responses of pallidal neurons to a normally excitatory 1 μ mol/kg dose of this agonist administered subsequently, was reconfirmed. Pretreatment with this ‘priming’ dose of apomorphine also attenuated the rate increases produced by d-amphetamine (8.7 μ mol/kg) and enhanced the rate inhibitory effects of haloperidol. The ‘priming’ effect appears related to the dopamimetic effects of apomorphine; a non-excitatory dose of a second dopamine agonist, lisuride (0.07 μ mol/kg i.v.), similarly blocked the effect of excitatory doses of lisuride (1 μ mol/kg i.v.) on pallidal activity

A microiontophoretic study of morphine on single neurons in the rat globus pallidus

The microiontophoretic application of morphine to single globus pallidus neurons in morphine naive rats resulted in a depression of both spontaneous and glutamate-evoked firing of these neurons. Seventy percent of all pallidal neurons on which morphine was tested exhibited some degree of depression of neuronal discharge; no excitatory effect was observed to morphine on any pallidal neurons. The depressant effects of morphine, but not those of dopamine, could be antagonized by the microiontophoretic application of the morphine antagonist naloxone, indicating that the morphine-induced depression of pallidal neuronal activity was a specific morphine action. This effect of morphine is most likely mediated by the opiate receptors on pallidal neurons that have been proposed to function in enkephalinergic-mediated synaptic transmission.

Effects of interruption of the nigrostriatal pathway and of dopaminergic agents on the spontaneous activity of globus pallidus neurons in the awake monkey

Interruption of the nigrostriatal pathway has been shown to change parameters of striatal activity. These changes are often difficult to explain because the functional structure of the striatum is not understood sufficiently. The function of the globus pallidus appears to be simpler. It transmits the output of the striatum to the thalamus and to the midbrain. Yet the effects of interruption of the nigrostriatal pathway on the activity of pallidal neurons are unknown. To study these effects the spontaneous activity of globus pallidus neurons was recorded in intact monkeys and in monkeys with lesions of the ventromedial midbrain tegmentum. The two groups of animals were studied with and without administration of dopaminergic agents. In intact monkeys medial pallidal neurons discharge uninterruptedly at high firing rates, while the discharge of most lateral pallidal neurons is interrupted by relatively long periods of silence. Lesions involving the nigrostriatal pathway change the firing patterns but not the mean firing rates of pallidal neurons. In lesioned monkeys pallidal neurons fire in bursts continuously: during movement, rest and sleepiness. Two lines of evidence strongly suggest that the bursting pallidal activities are a consequence of the interruption of the nigrostriatal dopaminergic pathway: (1) the percentage of bursting pallidal neurons is proportional to the amount of degeneration in the pars compacta of the ipsilateral substantia nigra; (2) chronic administration of dopamine antagonists, haloperidol and reserpine, reproduces in intact monkeys the bursting activities observed in lesioned animals. On the other hand, single injections of dopamine agonist, apomorphine and piribedil, silence the medial pallidum and concomittantly abolish the signs of parkinsonism displayed by lesioned monkeys.

Turnover times of gamma-aminobutyric acid and acetylcholine in nucleus caudatus, nucleus accumbens, globus pallidus and substantia nigra: effects of repeated administration of haloperidol

Neostriatal GABAergic neurons projecting to the globus pallidus synthesize the opioid peptide enkephalin, while those innervating the substantia nigra pars reticulata and the entopeduncular nucleus synthesize dynorphin. The differential control exerted by dopamine on the activity of these two efferent projections concerns also the biosynthesis of these opioid peptides. Using in situ hybridization histochemistry, we investigated the role of opioid co-transmission in the regulation of neostriatal and pallidal activity. The expression of the messenger RNAs encoding glutamate decarboxylase—the biosynthetic enzyme of GABA—and the precursor peptides of enkephalin (preproenkephalin) and dynorphin (preprodynorphin) were measured in rats after a sustained blockade of opioid receptors by naloxone (s.c. implanted osmotic minipump, eight days, 3 mg/kg per h), and/or a subchronic blockade of D2 dopamine receptors by haloperidol (one week, 1.25 mg/kg s.c. twice a day). The density of μ opioid receptors in the neostriatum and globus pallidus was determined by autoradiography. Naloxone treatment resulted in a strong up-regulation of neostriatal and pallidal μ opioid receptors that was not affected by the concurrent administration of haloperidol. Haloperidol alone produced a moderate down-regulation of neostriatal and pallidal μ opioid receptors. Haloperidol strongly stimulated the expression of neostriatal preproenkephalin and preprodynorphin messenger RNAs. This effect was partially attenuated by naloxone, which alone produced moderate increases in preproenkephalin and preprodynorphin messenger RNA levels. In the neostriatum, naloxone did not affect either basal or haloperidol-stimulated glutamate decarboxylase messenger RNA expression. A strong reduction of glutamate decarboxylase messenger RNA expression was detected over pallidal neurons following either naloxone or haloperidol treatment, but concurrent administration of the two antagonists did not result in a further decrease.The amplitude of the variations of μ opioid receptor density and of preproenkephalin and preprodynorphin messenger RNA levels suggests that the regulation of neostriatal and pallidal μ opioid receptors is more susceptible to a direct opioid antagonism, while the biosynthesis of opioid peptides in the neostriatum is more dependent on the dopaminergic transmission. The down-regulation of μ opioid receptors following haloperidol represents probably an adaptive change to increased enkephalin biosynthesis and release. The haloperidol-induced increase in neostriatal preprodynorphin messenger RNA expression might result from an indirect, intermittent stimulation of neostriatal D1 receptors. The haloperidol-induced decrease of pallidal glutamate decarboxylase messenger RNA expression suggests, in keeping with the current functional model of the basal ganglia, that the activation of the striatopallidal projection produced by the interruption of neostriatal dopaminergic transmission reduces the GABAergic output of the globus pallidus.The reduction of pallidal glutamate decarboxylase messenger RNA expression following opioid receptor blockade indicates an indirect, excitatory influence of enkephalin upon globus pallidus neurons and, consequently, a functional antagonism between the two neuroactive substances (GABA and enkephalin) of the striatopallidal projection in the control of globus pallidus output. Through this antagonism enkephalin could partly attenuate the GABA-mediated effects of a dopaminergic denervation on pallidal neuronal activity.

Activity of pallidal neurons during movement.

Activity of pallidal neurons during movement.

Effect of stimulation of the caudate nucleus on activity of neurons of the globus pallidus

Activity of neurons of the globus pallidus was recorded extracellularly during stimulation of the caudate nucleus. It is demonstrated that background activity (BA) of most neurons of the globus pallidus is depressed under these conditions, which is regarded as a manifestation of inhibition of the investigated neurons. The period of BA depression varied in different cells from 60 to 500 msec. In some cases this period was preceded by emergence of an action potential with a latent period of 10–20 msec. In addition to inhibition of the activity of globus pallidus neurons during stimulation of the caudate nucleus, it was possible to record evoked responses of the given neurons in the form of group discharges with a latent period of 18–40 msec and single action potentials with a latent period of 50–100 msec. The neurons that reacted with a shorter latent period were localized at the lateral limit of the globus pallidus, whereas neurons with other kinds of responses were distributed in the globus pallidus comparatively evenly.