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PubMed1989

Corticotropin-releasing factor stimulates the release of methionine-enkephalin and dynorphin from the neostriatum and globus pallidus of the rat: in vitro and in vivo studies.

This study examined the changes in the in vitro and in vivo release of methionine-enkephalin (Met-enkephalin), and dynorphin from the rat neostriatum in response to corticotropin-releasing factor (CRF). The levels of each opioid peptide were measured in the same sample collected at each time interval by specific radioimmunoassay methods. The in vitro release experiments were conducted using neostriatal slices (250 microns) obtained from adult male Wistar rats whereas in the in vivo studies, the release of both Met-enkephalin and dynorphin were assessed in push-pull perfusates of the caudate nucleus (containing both Met-enkephalin and dynorphin cell bodies/fibres) and the globus pallidus (containing Met-enkephalin and dynorphin terminals) of chloral hydrate-anaesthetised adult male Wistar rats. In the in vitro studies, CRF (10(-12), 10(-10) and 10(-8) M) (applied in pulses of 75 min) stimulated both Met-enkephalin and dynorphin release from the neostriatal slices in a dose-related manner; in the presence of the CRF receptor antagonist, alpha-helical CRF9-41 (10(-6) M) the release of both Met-enkephalin and dynorphin in response to CRF (10(-8) M) were completely blocked. Push-pull perfusion experiments conducted in both the caudate nucleus and the globus pallidus, also demonstrated a dose-related increase in the release of both Met-enkephalin and dynorphin in response to CRF (10(-12), 10(-10) and 10(-8) M) applied in 60-min pulses. In addition, in each of the two brain sites, the release of both Met-enkephalin and dynorphin in response to CRF (10(-8) M) was completely blocked by alpha-helical CRF9-41 (10(-6) M). Both the in vitro and in vivo studies thus demonstrate that CRF can exert potent effects on Met-enkephalin and dynorphin release within the neostriatum-pallidum of the rat and that such effects are mediated via receptors specific for CRF, probably located on both the cell bodies and terminals of these opioid-containing neurones. The data obtained in this study thus substantiate the view that CRF, in addition to its regulation of pituitary opioid peptides, can communicate to opioid-containing neurones within the central nervous system and that many of the effects elicited by CRF may be ascribed to the opioid peptide released by CRF.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1996

Morphologically distinct subpopulations of neurotensin-immunoreactive striatal neurons observed in rat following dopamine depletions and D2 receptor blockade project to the globus pallidus.

It has been reported in previous studies that perikaryal neurotensin immunoreactivity is largely absent in the rat striatum except following striatal dopamine depletion or blockade of dopamine D2 receptors, after which, however, neurotensin immunoreactivity is elicited in at least two distinct subpopulations of striatal neurons [Zahm D.S. (1992) Neuroscience 46, 335-350]. One subpopulation of such cells (type I), prominent following D2 receptor blockade, is located mainly in the matrix compartment in the rostral, dorsomedial and ventrolateral parts of the striatum, and comprises neurons at the large end of the medium-sized spectrum that exhibit intense neurotensin immunoreactivity in perikarya and proximal dendrites, but rarely display Fos immunoreactivity [Senger B. et al. (1993) Neuroscience 57, 649-660]. A second subpopulation (type II) resides predominantly in the patch (striosome) and matrix compartments in the dorsolateral quadrant of the striatum, and is prominent following administration of reserpine. These neurons are at the small end of the medium size range and exhibit very light neurotensin immunoreactivity, with little staining of dendrites. Fos immunoreactivity is frequently co-localized in striatal neurons that exhibit a type II striatal neurotensin response [Brog J.S. and Zahm D.S. (1995) Neuroscience 65, 71-86]. In the current study, neurotensin immunoreactivity was elicited in striatal neurons by ventral mesencephalic 6-hydroxydopamine lesions or administration of reserpine or haloperidol. Irrespective of which drug was given, retrogradely transported Fluoro-Gold was prominently co-localized with neurotensin-like immunofluorescence in the perikarya of striatal neurons following injections of the retrograde tracer into the globus pallidus. Few double-labeled neurons were observed following administration of any of these drugs and injections of Fluoro-Gold into the substantia nigra. It is concluded that two subpopulations of neurotensin-immunoreactive striatal neurons project predominantly to the globus pallidus and minimally to the substantia nigra.

Animals↗

PubMed2005

Parkinsonism following bilateral lesions of the globus pallidus: performance on a variety of motor tasks shows similarities with Parkinson's disease.

OBJECTIVES: The authors report the results of detailed investigations into the motor function of a patient who, after a heavy drinking binge and subsequent unconsciousness, respiratory acidosis, and initial recovery, developed parkinsonism characterised by hypophonic speech and palilalia, "fast micrographia", impaired postural reflexes, and brady/akinesia in proximal (but not distal) alternating upper limb movements. METHODS: In addition to brain magnetic resonance imaging (MRI), different aspects of motor function were investigated using reaction time (RT) tasks, pegboard and finger tapping tasks, flex and squeeze tasks, movement related cortical potentials (MRCPs), and contingent negative variation (CNV). Cognitive function was also assessed. The results were compared to those previously reported in patients with Parkinson's disease (PD). RESULTS: Brain MRI showed isolated and bilateral globus pallidus (GP) lesions covering mainly the external parts (GPe). These lesions were most probably secondary to respiratory acidosis, as other investigations failed to reveal an alternative cause. The results of the RT tasks showed that the patient had difficulties in preparing and maintaining preparation for a forthcoming movement. MRCP and CNV studies were in line with this, as the early component of the MRCP and CNV were absent prior to movement. The patient's performance on pegboard and finger tapping, and flex and squeeze tasks was normal when performed with one hand, but clearly deteriorated when using both hands simultaneously or sequentially. CONCLUSIONS: In general, the present results were similar to those reported previously in patients with PD. This provides further indirect evidence that the output of globus pallidus is of major importance in abnormal motor function in PD. The possible similarities of the functional status of GP in PD and our case are discussed.

Acidosis, Respiratory↗

PubMed2004

Behavioural disorders induced by external globus pallidus dysfunction in primates: I. Behavioural study.

The current model of basal ganglia organization postulates the existence of a functional partitioning into sensorimotor, associative and limbic territories, implicated in motor, cognitive and emotional aspects of behaviour, respectively. This organization was proposed initially on the basis of the cortico-striatal projections and was extended to the various structures of the basal ganglia. While there is a considerable body of experimental evidence in support of an involvement of the basal ganglia sensorimotor territory in basic control of movements, evidence for the functional relevance of the non-motor territories has had to be based on a growing number of clinical observations due to the paucity of relevant animal studies. Previous studies in monkeys have, however, shown that a reversible and focal dysfunction induced by microinjections of bicuculline in the sensorimotor territory of the external globus pallidus (GPe) can generate abnormal movements. We therefore hypothesized that the same approach applied to the associative and limbic territories of the GPe would induce behavioural disorders rather than abnormal movements. To address this hypothesis, we performed microinjections of bicuculline, using the same concentration in each of the sensorimotor, associative and limbic territories of the GPe, as defined by striato-pallidal projections. Spontaneous behaviour and performance of a simple food-retrieving task during the effects of these microinjections were compared with data obtained in control conditions in the same monkeys. We found that bicuculline microinjections induced stereotypy when performed in the limbic part of the GPe, and attention deficit and/or hyperactivity when performed in the associative part. No movement disorders were observed during these behavioural disturbances. As previously described, abnormal movements were observed when bicuculline was injected into the sensorimotor territory of the GPe. The relationship between the localization of microinjection sites and the type of behavioural effect was similar for the three monkeys. Control microinjections of bicuculline into surrounding structures (striatum and internal globus pallidus) and saline injections into the GPe failed to induce any observable effect. These results support the hypotheses of functional diversity and territorial specificity in the GPe, in agreement with the parallel circuits organizational model of the basal ganglia. Furthermore, the behavioural effects shared similar features with symptoms observed in Tourette's syndrome, attention deficit/hyperactivity and compulsive disorders. Thus, our study provides experimental evidence for the involvement of the associative and limbic parts of the basal ganglia in these pathologies. These results may provide the basis for a primate model of these disorders.

Animals↗

PubMedDate not supplied

[The realization of a conditioned avoidance reflex in rats under conditions of the multiple activation of the globus pallidus dopaminergic system].

Daily bilateral microinjections of 15 or 45 mcg of amphetamine into the globus pallidus of rats within three weeks inhibited the realization of conditioned avoidance in a shuttle-box. The dose of 15 mcg was most effective. There were no changes in locomotor activity. In contrast to the results obtained earlier in the experiments with similar neostriatal microinjections, no stimulatory dopaminergic effects (stereotyped behavior) were observed. The differences are discussed in the roles of the pallidal and neostriatal dopaminergic systems in regulation of behavior.

Amphetamine↗

PubMed1983

[Inhibition of the evoked liberation of (Met5)enkephalin from slices of globus pallidus in the presence of thiorphan and bestatin].

(Met5) enkephalin released from slices of Rat globus pallidus by 30 mM or 50 mM K+ is hydrolysed to the extent of 85% before reaching the incubation medium. When thiorphan and bestatin, two peptidase inhibitors, are added, this inactivation process is completely prevented but the peptide release from tissues is significantly diminished. The latter effect being reversed in the presence of an opioid antagonist, naloxone, in moderate concentration, the existence of an auto-inhibition process regulating enkephalin release is suggested.

Amino Acids, Sulfur↗

PubMed1994

Compartmental distribution of parvalbumin and calbindin D-28k in rat globus pallidus.

The cellular localization of parvalbumin (PV) and calbindin D-28k (CB) in the globus pallidus (GP) of rats was studied with double-immunohistochemical methods applied to single sections. The two calcium-binding proteins were found to be differentially distributed in GP. PV-positive cells were largely concentrated in the lateral part of GP where CB immunostaining was minimal. Their number and location varied along the rostrocaudal axis of GP. Pallidal PV cells were either large and multipolar or small and fusiform. In contrast, the medial part of GP was markedly enriched with CB neuropil but largely devoid of PV-positive cells. This spatial segregation indicates the existence of at least two different functional domains in the rat GP.

Animals↗

PubMed1991

Cholinergic neuronal loss in the globus pallidus of Alzheimer disease patients.

Cholinergic neurons of the ventral pallidum and the dorsal pallidum (globus pallidus) were immunohistochemically investigated in patients suffering from Alzheimer disease (AD). Measurement of cholinergic neurons, stained with an antiserum against choline acetyltransferase (ChAT), revealed that their number was significantly reduced in both the dorsal pallidum (37.5%) and the ventral pallidum (65%) of AD patients (n = 4) when compared to control subjects (n = 3). No shrinkage of these cells was observed. The number of immunostained neuropeptide Y-containing neurons in the same structures was not different in controls and AD patients, indicating that the loss of cholinergic neurons was selective. These results combined with previous reports give further information upon which specific subsets of cholinergic neurons degenerate in AD.

Aged↗

PubMed1988

Anterograde and retrograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) from the globus pallidus to the striatum of the rat.

Iontophoretic administration of PHA-L into the globus pallidus of rats resulted in the labeling of neuronal perikarya in the striatum as well as axons and terminals in the striatum, entopeduncular nucleus, subthalamus and substantia nigra. The labeled striatal perikarya were densely stained in Golgi fashion with virtually complete filling of the dendrites and spines. It is concluded that the striatal cells were filled by the retrograde transport of PHA-L and represent either striatopallidal cells, or striatonigral cells whose axons were interrupted as they passed through the injection site. The anterogradely labeled axon terminals in the striatum were observed in close apposition to the dendrites of the retrogradely labeled neurons suggesting the existence of synaptic contacts between the two groups of cells. This study demonstrates that PHA-L can be transported retrogradely as well as anterogradely following iontophoretic injections.

Animals↗

PubMed1983

Labeled norepinephrine uptake and release in rat globus pallidus.

The uptake and release of [3H]norepinephrine [( 3H]NE) were investigated using isolated rat globus pallidus slices to determine the possible neurotransmitter role of this catecholamine. The uptake into these slices was linear for the first 10 min. Kinetic analysis indicated two components of NE accumulation, one representing a high (Km1 2.9 X 10(-7) M and Vmax1 1.4 pmol/mg/10 min) and other a low (Km2 1.6 X 10(-6) M and Vmax2 5 pmol/mg/10 min) affinity uptake system. Desmethylimipramine at a concentration of 10(-5) M reduced the high affinity uptake of [3H]NE by 25% of the control values. Electrical stimulation of the slices increased the efflux of [3H]NE and its metabolites from tissues preloaded with [3H]NE, in a current- and frequency-dependent fashion. The release of [3H]NE and its metabolites induced by electrical stimulation (1 mA, 20 Hz, 1 ms for 2 min) was inhibited by tetrodotoxin (10(-6) M), and by a calcium-free medium containing EGTA (10(-4) M) or medium with a high magnesium-concentration (2 X 10(-2) M). These findings provide strong evidence for the neurotransmitter role of NE, in these tissues.

Animals↗

PubMed1999

Internal globus pallidus discharge is nearly suppressed during levodopa-induced dyskinesias.

The functional status of the globus pallidus internal segment (GPi) plays a key role in mediating the effects of antiparkinsonian drugs. During long-term levodopa therapy, patients develop abnormal movements, dyskinesias, the pathophysiological basis of which is poorly understood. We recorded single cells in the GPi of parkinsonian monkeys continuously through the "off" and "on" states, and 10 to 15 minutes later during "on with or without dyskinesias," depending on two doses of levodopa. The transition from the "off" to the "on" state was characterized by a decrease (most cells), no change, or an increase in firing rate of individual cells. During dyskinesias, firing rates declined profoundly in almost all cells, with decrements as low as 97% in individual cells. These changes occurred only when dyskinesias were present. The difference in GPi activity between "on" and "on with dyskinesias" suggests that normal motor function in Parkinson's disease critically depends on fine tuning of the basal ganglia output. Dyskinesias result from an imbalanced low GPi discharge, a circumstance that may be susceptible to development of new therapeutic approaches.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1984

Decreased cortical glucose utilization after ibotenate lesion of the rat ventromedial globus pallidus.

Rats received unilateral injections of ibotenic acid (12 micrograms) or vehicle in the ventromedial globus pallidus to lesion the primary source of cortical cholinergic innervation. At 3 or 28-32 days postinjection, the regional cerebral metabolic rate for glucose (rCMRglu) was measured by the 2-deoxy-D-[14C]glucose technique in nine cortical areas, the anterior thalamus, and the dorsal hippocampus. Effects of oxotremorine (0.1 mg/kg i.p.) on rCMRglu in these areas were assessed in ibotenic acid-lesioned and sham-treated rats. Significant effects of ibotenic acid injections and hemispheric asymmetries in rCMRglu were observed in all cortical areas (p less than or equal to 0.05), but not in the anterior thalamus or hippocampus. Cortical rCMRglu generally was lower in the lesioned hemisphere 3 days after ibotenic acid injections, but not after sham treatments. Hemispheric asymmetries were not apparent 28-32 days after pallidal lesions. Oxotremorine produced significant effects in the frontoparietal cortex and anterior thalamic nuclei. In the frontoparietal cortex, rCMRglu was 32% lower in the ibotenate-lesioned hemisphere as compared with the contralateral hemisphere. Oxotremorine did not eliminate hemispheric asymmetry, but increased rCMRglu in the lesioned frontoparietal cortex by 38%. Results support the views that cortical metabolic decrements in Alzheimer's disease are due in part to loss of subcortical cholinergic innervation and that muscarinic agonists may partially reverse these decrements.

Alzheimer Disease↗

PubMed1991

Intracellular study of rat globus pallidus neurons: membrane properties and responses to neostriatal, subthalamic and nigral stimulation.

Physiological properties of globus pallidus (GP) neurons were studied intracellularly in anesthetized rats. More than 70% of the neurons exhibited continuous repetitive firing of 2-40 Hz, while others exhibited periodic burst firing or no firing. The repetitively firing neurons exhibited the following properties: spike accommodation; spike frequency adaptation; continuous firing with a frequency of about 100 Hz generated by intracellular current injections; fast anomalous rectification; ramp-shaped depolarization upon injection of depolarizing current; and post-active hyperpolarization. The burst firing neurons evoked a large depolarization with multiple spikes in response to depolarizing current, and a similar response was observed after the termination of hyperpolarizing current. The few neurons which did not fire spontaneous spikes exhibited strong spike accommodation when they were stimulated by current injections. The continuously firing neurons were antidromically activated by stimulation of the neostriatum (Str) (23 of 68), the subthalamic nucleus (STh) (55 of 75), and the substantia nigra (SN) (25 of 46). The antidromic latencies of the 3 stimulus sites were very similar (about 1 ms). None of the burst firing neurons were antidromically activated. Three non-firing neurons evoked antidromic responses only after Str stimulation. Only repetitively firing neurons evoked postsynaptic responses following stimulation of the Str and the STh. Stimulation of the Str evoked initial small EPSPs with latencies of 2-4 ms and strong, short duration IPSPs with latencies of 2-12 ms. Stimulation of the STh evoked short latency EPSPs overlapped with IPSPs. Frequently, these responses induced by Str and STh stimulation were followed by other EPSPs lasting 50-100 ms. These results indicated: (1) that the GP contains at least 3 electrophysiologically different types of neurons; (2) that GP projections to the Str, the STh, and the SN are of short latency pathways; (3) that Str stimulation evokes short latency EPSPs followed by IPSPs and late EPSPs in GP neurons; and (4) that STh stimulation evokes short latency EPSPs overlapped with short latency IPSPs and late EPSPs in GP neurons.

Animals↗

PubMed1999

Direct stereotactic MRI location in the globus pallidus for chronic stimulation in Parkinson's disease.

We evaluated the direct location in the globus pallidus (GP) under stereotactic MRI (sMRI) guidance in five parkinsonians treated with chronic deep brain stimulation (four bilaterally). The sMRI consisted of three orthogonal (horizontal, frontal, sagittal) sets of images obtained with a stereotactic frame and its localiser. The sMRI was coupled with ventriculography to compare the location with the classic indirect method based on commissural landmarks. The target was defined on T2-weighted slices in the anterior part of the medial GP, at the vertex of the nucleus. It was reached via one track with a semi-micro-electrode and step by step high frequency stimulation, then replaced by a quadripolar electrode once we located the site enabling the optimal clinical improvement. Stereotactic x-rays localised the final position of the electrode. A company software matched sMRI, ventriculography, and peroperative (perop) x-rays, with reference to the stereotactic location boxes. We analysed the effects of acute (perop) and chronic (six-month follow-up) stimulation of active plots (acplots), i.e. leading to optimal clinical improvement. Three distances with reference to the acplots were measured both on sMRI and ventriculography: the laterality from the median sagittal plane of the third ventricle; the anterior position from the midpoint of the intercommissural line (Icl), and the vertical position with regard to the Icl. We then compared the differences in measurements (n = 64) with the Bland and Altman method. The mean difference was 0.09 mm with 95% of the values between +/- 1 mm, but only the laterality had a statistically significant agreement (all the differences included between +/- two times the standard deviation of the mean). The acplots distances from the dorsal, ventral, and medial boundaries of GP (defined by manual surrounding on frontal and horizontal planes) were measured on sMRI. With one exception, the acplots were all included in the nucleus. The six-month acplots were located dorsally with reference to the perop ones. Clinical benefit at six-months follow-up showed results comparable to the literature. Direct location of GP target based on sMRI seems a simple and reliable method.

Cerebral Ventriculography↗

PubMed2005

Globus pallidus volume is related to symptom severity in neuroleptic naive patients with schizophrenia.

This study compares globus pallidus (GP) volume between neuroleptic naive patients with schizophrenia and healthy controls using structural MRI. The volume of the external segment of the GP (GPe) was positively correlated with the severity of global symptoms, as measured by the Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms (SANS/SAPS, Andreasen and Olsen, 1982). The volume for the GP, GPe, and internal segment (GPi) did not differ between groups.

Adult↗

PubMed1975

Excitatory and inhibitory effects of globus pallidus and substantia nigra on the lateral hypothalamic activity in the rat.

Stimulation of the rat globus pallidus (GP) and substantia nigra (SN), while recording in the lateral hypothalamus, revealed mutual interconnections. Stimulation of GP produced an EPSP-IPSP sequence, while SN stimulation produced EPSP only. Antidromic LH spikes were obtained with either stimulation. Inhibitory interneurons responsible for the IPSP are located in the dorsolateral part of the LH. In the LH, only glucose sensitive neurons were specifically facilitated by SN stimulation and inhibited by GP stimulation. Dopamine and noradrenaline, applied electrophoretically to these neurons, yielded inhibition in a dose response manner, denying the possibility of dopamine as an excitatory transmitter substance. The mutual interrelationship between the LH and other centers, including the frontal cortex, may well influence motivation of feeding and other behavior.

Animals↗

PubMed1995

Multisensory convergence and integration in the neostriatum and globus pallidus of the rat.

The extracellular response properties of neurons in the caudate-putamen (CPu), globus pallidus (GP) and lateral amygdaloid nucleus (La) evoked by auditory and somatosensory stimuli were investigated. A total of 61 neurons in these areas responded either singly to somatosensory stimulation (unisensory), or to both somatosensory and auditory stimulation (multisensory). Higher rates of somatosensory stimulation reduced the response magnitude of CPu neurons more than that of GP neurons. In multisensory neurons, combined somatosensory and auditory stimulation compared to unisensory stimulation resulted in three characteristic response patterns: enhancement, depression or interaction. Temporal misalignment of the peak frequency latencies evoked by auditory and somatosensory stimulation altered the response magnitude in the majority of neurons. The response properties and anatomical connectivity of CPu and GP neurons suggest that the observed multisensory integrative effects may be used to facilitate motor responses to low intensity stimuli.

Acoustic Stimulation↗

PubMedDate not supplied

Vascular supply pattern to rat caudatoputamen and globus pallidus: scanning electronmicroscopic study of vascular endocasts of stroke-prone vessels.

The caudatoputamen (CP) and globus pallidus (GP) are supplied by vessels often involved with stroke in both rat and human. The pattern of vascular supply to the CP and GP in rat has, in contrast to humans, been only partially described. The vascular pattern to the rat CP and GP is described utilizing vascular endocasts and scanning electronmicroscopy in aging, normotensive rats. Endocasts were produced by intra-cardiac infusion of Batson's Corrosion Compound. The vascular pattern is complex, involving 1) recurrent vessels from the anterior cerebral artery, 2) branches from the arterial circle rostral or caudal to the origin of the middle cerebral artery (MCA), 3) up to 6 branches from the MCA, and 4) 2 major branches from the caudal part of the arterial circle. The vessels in groups 1--3 were serpentine, their luminal diameters abruptly reduced at branch points, and the angle of departure from the parent vessels approximated 90 degrees. These vessels supplied much of the CP and GP, while group 4 supplied the caudal CP with vessels arranged in a lattice-like fashion from the 2 penetrating parental arteries.

Animals↗