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PubMed2000

Unilateral lesions of the globus pallidus: report of four patients presenting with focal or segmental dystonia.

OBJECTIVES: To interpret clinical features after unilateral lesions of the globus pallidus on the basis of physiology of the basal ganglia. METHODS: Four patients with unilateral lesions in the globus pallidus (GP) were clinically examined and the literature on patients with pallidal lesions was reviewed. RESULTS: Three patients presented with contralateral dystonia largely confined to one arm in one case and one leg in two cases. One patient had predominant contralateral hemiparkinsonism manifested mainly as micrographia and mild dystonia in one arm. The cause of the lesions was unknown in two patients. In the other two symptoms had developed after head trauma and after anoxia. All lesions involved the internal segment of the GP. Two patients, including the patient with hemiparkinsonism, had additional involvement of the external segment of the GP. In the literature reports on 26 patients with bilateral lesions restricted to the GP only two with unilateral lesions were found. The patients with bilateral pallidal lesions manifested with dystonia, parkinsonism, or abulia. One of the patients with unilateral GP lesions had contralateral hemidystonia, the other contralateral arm tremor. CONCLUSION: These cases emphasise the importance of the GP, particularly its internal segment, in the pathophysiology of dystonia.

Adult↗

PubMed1985

Non-cholinergic globus pallidus cells that project to the cortex but not to the subthalamic nucleus in rat.

A substantial population of small globus pallidus neurons was demonstrated to have axonal projections to the cerebral cortex using fluorescent retrograde transport techniques. This population was separate from the more numerous population of medium size globus pallidus cells projecting to the subthalamic nucleus and was also separate from the pallidal and especially peripallidal population of large cholinergic cells projecting to the cortex. Some of the small, non-cholinergic cells projecting to the cortex also gave off axonal collaterals to the paraventricular thalamic nucleus.

Acetylcholinesterase↗

PubMed1995

Direct stereotactic targeting of the globus pallidus: an MRI-based anatomic variability study.

An anatomic variability study of the spatial relationship between the imaged globus pallidus, the optic tract, and the anterior and posterior commissures was performed using T1-weighted gradient echo three-dimensional volume acquisition MRI of 20 patients. Imaging data were resized, reformatted, and manually segmented for the above structures, and mean values and standard deviations for their medial, superior, lateral, and inferior limits determined. Findings demonstrate that the globus pallidus can be consistently and reliably imaged by MRI, that direct stereotactic targeting of this structure can account for normal anatomic variability which may be as much as several millimeters, and that the risk of injury to the optic tract may be reduced with this technique.

Adult↗

PubMed2000

Tropism of AAV-2 vectors for neurons of the globus pallidus.

A recombinant AAV-2 vector encoding the green fluorescent protein (gfp) under the control of the cytomegalovirus (CMV) promoter was injected into the striatum at varying antero-posterior coordinates. When the virus was delivered to the anterior part of the striatum, transduction efficiency was low and limited to the vicinity of the needle tract. In contrast, after injection into the posterior part of the striatum, in addition to a localized transduced area in the striatum, efficient and widespread transduction was observed at distance from the injection site, in the globus pallidus. In the latter case, labelled cells were also detected in the internal capsule and in the stria terminalis. The number of transduced cells in the striatum increased up to I month and then decreased whereas in the globus pallidus, transduction was maximal as early as 2 weeks post-injection. In the striatum and in the globus pallidus, the labelled cells had a neuron-like morphology. In contrast, in the internal capsule, labelled cells had a glial-like morphology.

Animals↗

PubMed1997

Effects of apomorphine on globus pallidus neurons in parkinsonian patients.

Current hypotheses of basal ganglia dysfunction in Parkinson's disease (PD) propose that neuronal hypoactivity in the globus pallidus externus (GPe), and hyperactivity in the output nuclei and the external and internal portions of the globus pallidus internus (GPi,e and GPi,i, respectively), result in the cardinal symptoms of PD. To test this theory, the nonselective D1- and D2-dopamine receptor agonist apomorphine (30-100 microg/kg SC) was administered to 14 levodopa-responsive PD patients who were off medication ("off" state) while recording neurons in GP. For 15 neurons that were continuously monitored, apomorphine was found to increase the firing rate of 3 neurons in GPe, and decrease the rate of 12 in GPi. The mean firing rates of many different neurons were determined before (n = 285) and at various intervals after (n = 184) the injection of the drug. The mean rates before apomorphine were as follows: GPe, 45 Hz (SD 15, n = 85); GPi,e, 67 Hz (SD 14, n = 125); and GPi,i, 85 Hz (SD 19, n = 75). At 25 to 35 minutes after APO, the rate of GPe neurons had increased to 72 Hz (SD 18, n = 7), the rate of GPi,e neurons had decreased to 39 Hz (SD 15, n = 15), and in GPi,i the rate decreased to 34 Hz (SD 22, n = 18). Eighty minutes after apomorphine administration, the mean firing rates returned to preadministration values. This study supports current models of basal ganglia dysfunction in PD and suggests that the therapeutic effect of apomorphine results from a normalization of the imbalance of neuronal activity in the direct and indirect pathways.

Action Potentials↗

PubMed1983

The comparison between enkephalin-like and dynorphin-like immunoreactivity in both monkey and human globus pallidus and substantia nigra.

The distribution of [Met]-Enkephalin and Dynorphin-like immunoreactivity were studied in the monkey and human globus pallidus and substantia nigra. These distributions were compared to those seen in these structures of the rat. Interspecies variations were observed in the substantia nigra, and in both pallidal segments. Differences between the distribution of the two opiate peptides occurred mostly in the limbic-related globus pallidus.

Animals↗

PubMed2004

Changes in extracellular dopamine in the rat globus pallidus induced by typical and atypical antipsychotic drugs.

Typical antipsychotic drugs with a high extrapyramidal motor side-effects liability markedly increase extracellular dopamine in the caudate-putamen, while atypical antipsychotic drugs with a low incidence of extrapyramidal motor side-effects have less pronounced stimulating actions on striatal dopamine. Therefore, it has been suggested that the extrapyramidal motor side-effects liability of antipsychotic drugs (APD) is correlated with their ability to increase extracellular dopamine in the caudate-putamen. The globus pallidus (GP) is another basal ganglia structure probably mediating extrapyramidal motor side-effects of typical antipsychotic drugs. Therefore, the present study sought to determine whether extracellular dopamine in the globus pallidus might be a further indicator to differentiate neurochemical actions of typical and atypical antipsychotic drugs. Using in vivo microdialysis we compared effects on pallidal dopamine induced by typical and atypical antipsychotic drugs in rats. Experiment I demonstrated that systemic administration of haloperidol (1 mg/kg; i.p.) and clozapine (20 mg/kg; i.p.) induced a significant pallidal dopamine release to about 160 and 180% of baseline, respectively. Experiment II revealed that reverse microdialysis of raclopride and clozapine using a cumulative dosing regimen did not stimulate extracellular dopamine in the globus pallidus if low (1microM) or intermediate (10 and 100 microM) concentrations were used. Only at a high concentration (1,000 microM), raclopride and clozapine induced a significant pallidal dopamine release to about 130 and 300% of baseline values, respectively. Thus, effects of typical and atypical antipsychotic drugs on pallidal dopamine were similar and thus, may not be related to their differential extrapyramidal motor side-effects liability. Furthermore, the finding that reverse microdialysis of raclopride over a wide range of concentrations did not stimulate pallidal dopamine concentrations tentatively suggests that pallidal dopamine release under basal conditions is not regulated by D2 autoreceptors.

Animals↗

PubMed2000

Decreased mu-opioid receptor binding in the globus pallidus of rats treated with chronic haloperidol.

RATIONALE: Chronic neuroleptic treatment produces a movement disorder in rats characterized by vacuous chewing movements (VCMs). Neuroleptics also produce a variety of changes in opioid neurotransmission in several regions of the basal ganglia. Rats with the VCM syndrome show elevated mRNA for enkephalin in striatopallidal neurons, suggesting a possible role for enkephalin in the pathophysiology of VCMs. OBJECTIVE: This study investigated the role of mu-opioid receptor density in the basal ganglia on the expression of VCMs. METHODS: Rats were treated with haloperidol for 24 weeks and withdrawn for 9 weeks. Mu (m) receptors were labeled with [3H]-DAMGO. RESULTS: Haloperidol treatment produced a significant reduction in mu-receptor binding in the globus pallidus (P<0.05). There was, however, no relationship between mu-opioid receptor density and VCMs in this or any other region of the basal ganglia. CONCLUSION: These results replicate prior findings of a neuroleptic-induced reduction in [3H]-DAMGO binding in the globus pallidus. The lack of association between VCMs and [3H]-DAMGO binding in the globus pallidus or any other region suggests that prior reports of enkephalinergic mRNA changes in the striatum are not accompanied by compensatory changes in postsynaptic neurons.

Animals↗

PubMed1989

Anatomically distinct output channels of the caudate nucleus and orofacial dyskinesia: critical role of the subcommissural part of the globus pallidus in oral dyskinesia.

The findings in this feline study indicate that the enkephalin-positive subcommissural part of the globus pallidus, which is known to contain GABA and cholinergic cells projecting to the cortex, is innervated by the anterodorsal region of the caudate nucleus, but not by the core. Like stimulation of a particular subclass of dopamine receptors in the anterodorsal region of the caudate nucleus, inhibition of the GABA receptors in the noted part of the globus pallidus resulted in orofacial dyskinesia, viz. tic-like contractions of the facial, eye and ear muscles, and tongue protrusions. This phenomenon was elicited by intrapallidal injections of the GABA antagonist picrotoxin in a dose-dependent manner and could be attenuated by the GABA agonist muscimol. Previous studies have already shown that neither stimulation of the dopamine receptors in the core of the caudate nucleus nor any manipulation with the first- and second-order output-stations of the latter brain region, viz. (a) those regions of the substantia nigra, pars reticulata which receive afferents from the caudate nucleus, and (b) those regions of the intermediate layers of the superior colliculus which receive afferents from the latter nigral region, ever resulted in orofacial dyskinesia. These findings support the hypothesis that the anatomically distinct input-output channels of the caudate nucleus are differentially involved in orofacial dyskinesia. The clinical impact of these findings is discussed in view of the L-3,4-dihydroxyphenylalanine-induced tardive dyskinesia in man. In addition, the relevance of the anatomical data is discussed in view of the co-occurrence of Parkinson's Disease and Dementia of Alzheimer-type in certain patients.

Animals↗

PubMed1999

Multisecond oscillations in firing rate in the globus pallidus: synergistic modulation by D1 and D2 dopamine receptors.

The firing rates of many basal ganglia neurons recorded in awake rats oscillate at seconds-to-minutes time scales, and the D1/D2 agonist apomorphine has been shown to robustly modulate these oscillations. The use of selective D1 and D2 antagonists suggested that both these receptor subfamilies are involved in apomorphine's effects. In the present study, spectral analysis revealed that baseline multisecond oscillations were significantly periodic in 71% of globus pallidus neurons. Baseline oscillations had a wide range of periods within the analyzed range, with a population mean of 32 +/- 2 s. Administration of the D1 agonist SKF 81297 (6-chloroPB) at 1.0 or 5.0 mg/kg significantly changed these oscillations, reducing means of spectral peak periods to 14 to 16 s (i.e., increasing oscillatory frequency). This effect was attenuated by D2 antagonist pretreatment. The D2 agonist quinpirole did not cause a significant population change in multisecond periodicities. The strongest effects on multisecond periodicities occurred after combined treatment with SKF 81297 and quinpirole. Low, ineffective doses of SKF 81297 and quinpirole, when combined, produced a significant increase in oscillatory frequency. Also, when quinpirole was administered after an already effective dose of SKF 81297, quinpirole shifted oscillations to an even faster range (typically to periods of <10 s). The dopaminergic control of multisecond periodicities in globus pallidus firing rate demonstrates D1/D2 receptor synergism, in that the effects of D1 agonists are potentiated by and partially dependent on D2 receptor activity. Modulation of multisecond oscillations in firing rate represents a novel means by which dopamine can influence globus pallidus physiology.

Animals↗

PubMed1978

In vitro release of [5-methionine]enkephalin and [5-leucine]-enkephalin from the rat globus pallidus.

Endogenous [5-methionine]enkephalin (Metenkephalin) and [5-leucine]enkephalin (Leu-enkephalin) are released from perfused slices of rat globus pallidus by increased K(+) in a Ca(2+)-dependent manner. Tissue perfused for 40 min contained only 26% of the Met-enkephalin and 44% of the Leu-enkephalin found in the freshly dissected tissue. After perfusion, the mean (+/-SEM) ratio (wt/wt) of Met-enkephalin to Leu-enkephalin was 3.4 +/- 0.2 compared with 5.8 +/- 0.2 in the fresh tissue. The degradation of trace amounts of synthetic [(3)H]enkephalins in the perfusing medium during stimulated release seems to reflect the accelerated degradation of enkephalin released from the tissue: 63% of the Met-enkephalin and 23% of the Leu-enkephalin were degraded in a medium containing bacitracin (30 mug/ml). The mean ratio (wt/wt) of the Met-enkephalin to the Leu-enkephalin recovered after release by exposure of slices to 50 mM K(+) was 2.7 +/- 0.3. When perfusates were corrected for degradation, this ratio increased to about 5.5 which is higher than that found in the perfused tissue. The differences in release, tissue loss, and catabolism of the two enkephalins may be reflecting differences in the metabolic systems operating on the pentapeptides, but this interpretation will have to be validated by in vivo release experiments. In any event these observations strongly suggest that both enkephalins can be considered candidate neurotransmitters in the rat globus pallidus.

Animals↗

PubMed1993

Subthalamic nucleus lesion regularizes firing patterns in globus pallidus and substantia nigra pars reticulata neurons in rats.

Subthalamic nucleus lesion altered the statistical properties of the firing patterns of globus pallidus and substantia nigra pars reticulata neurons recorded in urethane anesthetized rats by increasing the proportion of cells in both structures that fired with a very highly regular pattern (from approximately 25% to approximately 50%). In all cases, the most regularly firing neurons fired at a higher mean rate than did more slowly firing neurons. In contrast, globus pallidus lesion shifted the pattern of substantia nigra neurons towards more irregular firing and induced a bursty pattern in two neurons.

Action Potentials↗

PubMed1992

Effects of nigrostriatal lesions on the levels of messenger RNAs encoding two isoforms of glutamate decarboxylase in the globus pallidus and entopeduncular nucleus of the rat.

The neurotransmitter gamma-aminobutyric acid (GABA) is present in efferent neurons of the striatum and of the pallidum, one of the main striatal target areas. Dopaminergic nigrostriatal neurons play a critical role in the regulation of GABAergic neurotransmission in the striatum. In the present study, we investigated their role in the regulation of glutamate-decarboxylase (GAD) mRNA expression in two divisions of the pallidum in rats: the globus pallidus and entopeduncular nucleus, equivalent to the external and internal pallidum, respectively, of primates. Dopaminergic neurons were lesioned by unilateral injections of 6-hydroxydopamine (6-OHDA) in the substantia nigra of adult rats. Two or 3 weeks after the lesion, frontal cryostat-cut sections of the brain were processed for in situ hybridization histochemistry with 35S-labeled RNA probes synthesized from cDNAs encoding two distinct isoforms of GAD of respective molecular weight 67,000 (GAD67) and 65,000 (GAD65). The number of labeled cells was determined, and intensity of labeling in individual cells was analyzed by computerized image analysis on emulsion radioautographs. In the globus pallidus, the number of labeled neurons and intensity of labeling per cell were increased on the side ipsilateral to the lesion as compared with control rats in sections hybridized with the GAD67 RNA probe. No changes were detected on the side contralateral to the lesion or in the levels of labeling for GAD65 mRNA. Confirming previous data, the level of labeling for GAD65 mRNA was much higher than for GAD67 mRNA in the entopeduncular nucleus of control rats. In rats with a 6-OHDA lesion, labeling for both GAD67 and GAD65 mRNAs was decreased on the side contralateral, but not ipsilateral, to the lesion, as compared with control rats. The results show that lesions of the nigrostriatal pathway in rats affect the levels of mRNAs encoding two distinct isoforms of GAD in neurons of the globus pallidus and entopeduncular nucleus differently. In addition, results in the entopeduncular nucleus further support a bilateral effect of unilateral dopaminergic lesions.

Animals↗

PubMed1999

[Disappearance of globus pallidus hyperintensity in a patient with portal-systemic encephalopathy after occlusion of the shunt vessel].

A 67-year-old woman was admitted to our hospital with confusion and asterixis on January 23, 1994. She had had the same symptoms repeatedly. On admission she was disorientated, and had slurred speech and asterixis. Laboratory data showed hyperammonemia (84 micrograms/dl) with a poor ICG hepatic clearance (ICG15min = 32%), although hepatic failure did not exist. Abdominal ultrasonography, CT scan and liver biopsy showed no evidence of cirrhosis. Celiac arteriography revealed a large shunt vessel connecting the portal vein to the left renal vein. A 1.5 T magnetic resonance imaging (MRI) demonstrated a bilateral and symmetrical hyperintensity of the globus pallidus in the T1-weighted images. Portal-systemic encephalopathy recurred repeatedly in spite of the conservative therapy, and there was no evidence of the portal hypertension. Therefore, the operative procedure of ligation of the shunt vessel was done on February 21, 1995. After the operation, blood ammonia level and ICG hepatic clearance were normalized. She became free from encephalopathy. Twenty-seven months after the operation, the hyperintensity of the globus pallidus in the T1-weighted images completely disappeared. There have been several reports describing that the globus pallidus alterations on the T1-weighted images in patients with liver cirrhosis, manganese intoxication and portal-systemic encephalopathy. To our knowledge, this is the first case that the hyperintense signal of the basal ganglia in a patient with portal-systemic encephalopathy disappeared completely after occlusion of the shunt vessel.

Aged↗

PubMed1983

An intracellular HRP study of the rat globus pallidus. II. Fine structural characteristics and synaptic connections of medially located large GP neurons.

In order to classify the presynaptic elements contacting the principle class of globus pallidus neurons, electron microscopic examination of serial sections made from a medially located large globus pallidus neuron, labeled with intracellular horseradish peroxidase, was undertaken. In addition, the use of labeled and light microscopically reconstructed material allowed us to quantitatively determine the distribution of each bouton type along the soma and dendrites. Six types of presynaptic terminals contacting the labeled cell have been recognized. Type 1 endings, the most numerous (84%), make symmetrical contacts on all portions of the cell, except spines, contain large pleomorphic, and a few large dense-core vesicles. Type 2 endings are filled with small spherical-to-ellipsoidal synaptic vesicles. They make asymmetrical contacts only with higher-order dendrites and account for 12% of synaptic contacts onto the labeled neuron. Type 3 endings are large, contain sparsely distributed large pleomorphic vesicles, and make two symmetrical synapses per bouton, one onto a spine head and the other onto the underlying dendritic shaft. They are infrequent (0.2%), being found only in association with dendritic spines. Type 4 endings contain large pleomorphic synaptic vesicles and no dense-core vesicles. They make symmetrical contacts with the short primary dendrites. Type 5 endings contain a mixture of small clear pleomorphic vesicles and numerous large dense-core vesicles. They contact only the cell body and the short primary dendrites, making up 20% of somatic synaptic contacts but less than 1% of contacts onto dendrites. Type 6 boutons contain oval and flattened synaptic vesicles and establish symmetrical contacts with higher-order dendritic branches and the cell body.

Animals↗

PubMed1982

Somatosensory properties of globus pallidus neurons in awake cats.

The somatosensory properties of globus pallidus (GP) neurons were assessed in awake restrained cats. Forty-two percent of GP units responded to stimulation of the face. Receptive fields were typically bilateral (49%) or contralateral and 75% included perioral tissues. Responsive units showed little ability to encode force. In contrast, cells were sensitive to changes in stimulus location within the receptive zone. The majority of cells so tested showed enhanced responding to stimuli applied within the perioral zone. Many (42%) of the cells which responded to brushing of the guard hairs or vibrissa were directionally sensitive. Of those, 89% showed enhanced responding to stimuli which moved toward the front of the mouth. These data were discussed in relation to a role of the GP in feedback regulated head positioning movements.

Animals↗

PubMed1993

A histometrical study on the globus pallidus in Huntington's disease.

Pathological change of the globus pallidus (GP) in 6 cases of Huntington's disease (HD) was examined histometrically by comparison with 10 normal control cases. All but 1 case of HD were in late stages of the disease. Total neuronal count, area of GP, and neuronal cell density were measured in 5 selected regions of coronal sections taken along the antero-posterior axis. Contrary to the findings of previous reports, no neuronal depletion was recognized in HD in any region despite marked atrophy of tissue bulk. The atrophy was more severe in the external segment (GPe) than in the internal segment (GPi). Reactive astrocytosis and fibrillary gliosis were observed in the atrophic lesions. These results indicate that atrophy of the GP can be attributed to striato-pallidal fiber loss and not to neuronal depletion even in the late stages. These findings support the hypothesis that loss of striato-GPe fibers plays the most important role in choreic movements in HD. It remains to be determined whether the pallidal neurons are also preserved in the end stage of the disease.

Adult↗

PubMed1978

[Connections between the globus pallidus and putamen and the hypothalamus and subthalamus].

In 16 adult cats with electrolytically destructed external and internal parts of the globus pallidus and in 8 cats with destructed putamen direct strio-pallido-hypothalamic and strio-pallido-subthalamic pathways have been studied. Degeneration of the axonal preterminals and terminals have been examined in preparations treated after Nauta--Gygax, Nauta--Laidlow, Finck--Heimer with simultaneous additional staining of the nuclei with cresyl violet after Kawamura--Niimi. Direct pallido- and putamen-hypothalamic pathways to nuclei of the grey tubercle, posterior and lateral nuclei of the hypothalamus were stated. Direct pathways from the putamen to the subthalamic nucleus have been revealed, however, these pathways are represented in less degree than those of pallido-subthalamic connections. Direct pathways from the external portion of the globus pallidus and putamen to the subthalamic nucleus are more pronounced and represented by greater numbers of projections than those of strio-pallido-hypothalamic origin.

Animals↗