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PubMed1997

Differing influences of dopamine agonists and antagonists on Fos expression in identified populations of globus pallidus neurons.

Dopamine agonists increase the activity of globus pallidus neurons, as shown electrophysiologically and with Fos expression. More recently it has been shown that decreased D2 receptor activity also causes pallidal Fos expression. Similar responses occur in the striatum, where both dopamine agonists and D2 blockade induce Fos, although in separate neuronal populations (i.e. striatonigral and -pallidal). The present experiments investigate the possible differential dopaminergic regulation of Fos within pallidal neuronal populations, which were classified as parvalbumin-positive or -negative (with parvalbumin immunostaining), or as projecting to various target nuclei (with retrograde transport of FluoroGold iontophoresed into these nuclei). Rats with prior nigrostriatal lesions received saline, D1 agonist, or D2 agonist. Rats with no lesions received saline, combined D1/D2 agonists, or the D2 antagonist eticlopride. Two hours after drug injection, rats were perfused and their brains processed for double-labeling: either Fos staining with parvalbumin staining, or Fos or parvalbumin staining in FluoroGold-labeled sections. Overall, dopamine drug treatments induced more Fos in parvalbumin-negative than -positive cells. However, unlike dopamine agonists, eticlopride induced significant Fos only in the parvalbumin-negative cells. Dopamine agonist-induced Fos was found in pallidal neurons projecting to each of the target nuclei examined, in both normal and nigrostriatal-lesioned rats. Eticlopride-induced Fos occurred only in pallidal neurons projecting to the striatum, providing functional evidence for pallidostriatal cells without axon collaterals to other nuclei. It was also found that pallidostriatal neurons were distinguished from other projection populations by a relative lack of parvalbumin immunoreactivity. Pallidal cells respond heterogeneously to dopaminergic treatments based on their projection target and expression of parvalbumin. The smaller Fos responses in parvalbumin-containing cells may be due largely to the calcium buffering by the parvalbumin itself. Also, the pattern of Fos expression in pallidostriatal neurons suggests that dopamine regulates activity in these cells differently than in other projection populations.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Early postnatal development of the monkey globus pallidus: a Golgi and electron microscopic study.

The globus pallidus of 20 monkeys ranging in age from newborn to 4 months was examined in Golgi-impregnated material and ultrastructurally. There was no discernible difference between the lateral and medial segments of the structure. At the light microscope level, all neuronal types described in the adult are found at birth. The most common, the large fusifom cell, shows initial signs of immaturity such as blunt protrusions and dendritic dilations at bifurcation points, as well as growth cones, filopodia, and filiform processes. These features become more rare with age, and by 4 months, the neurons appear fully mature save for the terminal dendritic arborizations which are still underdeveloped. From the earliest ages examined, the large globular cells and the interneurons are more mature than the previous type. The afferent radial fibers of striatal origin are observed from birth, but they are grouped in bundles only after 8 weeks. The density of their climbing branches increases over time, reaching a mature appearance by 16 weeks. Afferents entering from the ventral surface do not yet show clusters of varicosities at 2 weeks. At the latter age, plexuses of fine beaded fibers are already seen covering large extensions of the nucleus. The fine structure correlates well with the Golgi material. The basic features of the neuropil are present at birth, albeit with immature characteristics such as the incomplete covering of the dendrites with axonal boutons and the low level of myelination of the radial fibers. Growth cones and profiles with signs of degeneration are observed during the first month. In the early ages examined, most dendrites show large varicosities and protrusions, some of which are spinelike and can be postsynaptic to multiple terminals. The other dendritic type, with only an occasional axodendritic synapse, is also seen from birth and increases in size as a function of time. The type I axonal boutons, of probable striatal origin, are quite immature at birth, and their characteristic interdigitations are seen only after the first week. The type II, III, IV, and V boutons appear mature at all ages examined but crest synapses formed by the type III terminals are observed in the later stages of the study. Finally, postsynaptic vesicle-containing profiles are present at 4 weeks, but triadic synaptic arrangements are formed only by 16 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Two new monoclonal antibodies provide immunohistochemical evidence for the unique biochemical similarity of the mouse globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata.

Similarities in cellular morphology, afferentation, efferentation, and neurotransmitter content between the internal and external parts of the pallidum and the substantia nigra pars reticulata have long been noted. Here we present evidence that the globus pallidus, entopedunucular nucleus and substantia nigra pars reticulata are more closely related to each other antigenically than to any other anatomical subdivision in the murine central nervous system. In a monoclonal antibody library composed of 20 distinctive lines selected from 300 hybridomas screened immunohistochemically on mouse brain sagittal sections we found two antibodies whose staining patterns distinguish the pallidum and substantia nigra pars reticulata from all other brain gray matter regions but stain these two divisions similarly. One monoclonal antibody, F1-134, stains all brain gray matter regions moderately but gives intense staining of the globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata only. Another monoclonal antibody, F1-20, stains different brain gray matter regions to varying degrees but shows a complete and exclusive exclusion of staining from the globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata. These results support the tripartite pallidum hypothesis. This study also provides an example of how the monoclonal antibody library strategy can be applied to general problems of brain organization.

Animals↗

PubMed2000

Lesion of the subthalamic nucleus or globus pallidus does not cause chaotic firing patterns in basal ganglia neurons in rats.

The basal ganglia appears to play an important role in behavioral selection. One model (Berns and Sejnowski's) of basal ganglia function argues that the subthalamic nucleus plays a critical role in this selection process and predicts that the subthalamic nucleus prevents the basal ganglia and its re-entrant circuits with the thalamus and cerebral cortex from developing chaotic oscillations. We tested this prediction by generating three-dimensional sequential interval state space plots of the spike trains from 684 globus pallidus, substantia nigra pars reticulata and subthalamic neurons recorded in intact, subthalamic lesioned and globus pallidus lesioned rats, neurons which had previously been analyzed with more standard statistical methods. Only 1 neuron (a globus pallidus neuron in a subthalamic lesioned rat) of the 684 showed a chaotic attractor. In no case did subthalamic nucleus lesion induce a chaotic firing pattern elsewhere in the basal ganglia.

Action Potentials↗

PubMed2006

Microelectrode-guided implantation of deep brain stimulators into the globus pallidus internus for dystonia: techniques, electrode locations, and outcomes.

OBJECT: Deep brain stimulation (DBS) of the globus pallidus internus (GPI) is a promising new procedure for the treatment of dystonia. The authors describe their technical approach for placing electrodes into the GPI in awake patients with dystonia, including methodology for electrophysiological mapping of the GPI in the dystonic state, clinical outcomes and complications, and the location of electrodes associated with optimal benefit. METHODS: Twenty-three adult and pediatric patients with various forms of dystonia were included in this study. Baseline neurological status and DBS-related improvement in motor function were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The implantation of DBS leads was performed using magnetic resonance (MR) imaging-based stereotaxy, single-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. Electrode locations were measured on computationally reformatted postoperative MR images according to a prospective protocol. CONCLUSIONS: Physiologically guided implantation of DBS electrodes in patients with dystonia was technically feasible in the awake state in most patients, and the morbidity rate was low. Spontaneous discharge rates of GPI neurons in dystonia were similar to those of globus pallidus externus neurons, such that the two nuclei must be distinguished by neuronal discharge patterns rather than rates. Active electrode locations associated with robust improvement (> 70% decrease in BFMDRS score) were located near the intercommissural plane, at a mean distance from the pallidocapsular border of 3.6 mm.

Adolescent↗

PubMed1999

Differential regulation of AP-1 DNA-binding activity by D1 and D2 dopamine receptor antagonists in the rat caudate-putamen and globus pallidus following a unilateral 6-OHDA lesion of the medial forebrain bundle.

The effect of D1 and D2 dopamine receptor antagonists on the DNA-binding activity of the AP-1 transcription factor was studied in the rat caudate-putamen and globus pallidus following a unilateral 6-OHDA lesion of the medial forebrain bundle. In the caudate-putamen, vehicle-treated rats showed increased AP-1 DNA-binding activity, which appeared to be reversed completely by treatment with the D1 receptor antagonist SCH23390 (1 mg kg-1 i.p.) and partially by the D2 antagonist sulpiride (50 mg kg-1 i.p.). In the globus pallidus, vehicle and sulpiride did not induce AP-1, while SCH23390 increased it significantly. This induction was much more prominent in the 6-OHDA-lesioned hemisphere than in the intact hemisphere. The present study suggests that in the caudate-putamen, dopamine-depletion induces long-lasting enhancement of AP-1 DNA-binding activity via activation of D1 receptors and the simultaneous activation of D2 receptors facilitate it. However, in the globus pallidus of the 6-OHDA-lesioned hemisphere, D1 but not D2 antagonism induces AP-1 in certain cell populations which may be distinct from those expressing AP-1 upon stimulation of D2 receptors.

Animals↗

PubMed2004

Microelectrode-guided implantation of deep brain stimulators into the globus pallidus internus for dystonia: techniques, electrode locations, and outcomes.

Object. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a promising new procedure for the treatment of dystonia. The authors present their technical approach for placement of electrodes into the GPi in awake patients with dystonia, including the methodology used for electrophysiological mapping of the GPi in the dystonic state, clinical outcomes and complications, and the location of electrodes associated with optimal benefit. Methods. Twenty-three adult and pediatric patients who had various forms of dystonia were included in this study. Baseline neurological status and improvement in motor function resulting from DBS were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Implantation of the DBS lead was performed using magnetic resonance (MR) imaging-based stereotaxy, single-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. Electrode locations were measured on computationally reformatted postoperative MR images according to a prospective protocol. Conclusions. Physiologically guided implantation of DBS electrodes in patients with dystonia is technically feasible in the awake state in most cases, with low morbidity rates. Spontaneous discharge rates of GPi neurons in dystonia are similar to those of globus pallidus externus neurons, such that the two nuclei must be distinguished by neuronal discharge patterns rather than by rates. Active electrode locations associated with robust improvement (> 50% decrease in BFMDRS score) were located near the intercommissural plane, at a mean distance of 3.7 mm from the pallidocapsular border. Patients with juvenile-onset primary dystonia and those with the tardive form benefited greatly from this procedure, whereas benefits for most secondary dystonias and the adult-onset craniocervical form of this disorder were more modest.

Adolescent↗

PubMed2000

Manganese deposition in the globus pallidus in patients with biliary atresia.

BACKGROUND: Chronic liver diseases may alter trace element contents in the brain. Among these trace elements, manganese is a ubiquitous transition metal excreted by the liver into the bile. Blood concentrations of manganese are elevated in patients with biliary atresia who have undergone hepatic portoenterostomy. The present study investigated the effects of liver transplantation on manganese deposition in the brain in such patients. METHODS: The signal intensity of the globus pallidus was calculated as an index defined as the percentile ratio of signal intensity in the globus pallidus to the subcortical frontal white-matter in sagittal T1-weighted magnetic resonance imaging planes. RESULTS: Brain magnetic resonance imaging revealed hyperintense signals in the globus pallidus due to manganese deposition in biliary atresia patients. Few neurologic symptoms related to manganese intoxication were observed. However, one 23-year-old female with biliary atresia had depressive symptoms and dyskinesia; she improved after oral administration of the dopamine precursor, L-DOPA. Manganese deposition disappeared in two patients after living-related reduced-size hepatic transplantation. CONCLUSIONS: Manganese accumulates in the brain during cholestasis associated with biliary atresia and disappears after hepatic transplantation. Manganese deposition is likely to be subclinical and reversible but may be associated with some age-related neurologic symptoms.

Adult↗

PubMed1994

High-intensity proton and T2-weighted MRI signals in the globus pallidus in juvenile-type of dentatorubral and pallidoluysian atrophy.

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder. An expanded CAG trinucleotide repeat sequence motif in a gene on the short arm of chromosome 12 has recently been identified in patients with DRPLA. Juvenile-type DRPLA is characterized by childhood onset and progressive myoclonic epilepsy (PME). According to the pathological study, the degeneration of the globus pallidus is more marked in this than in other types. We observed high-intensity signals in the globus pallidus on proton and T2-weighted magnetic resonance imaging (MRI) in a patient clinically diagnosed as juvenile-type DRPLA who had the expanded CAG trinucleotide repeat motif in the DRPLA gene. The globus pallidus may be affected in the early stages of this type of DRPLA, and MRI may be useful for the early diagnosis of DRPLA.

Atrophy↗

PubMed2006

Substantia nigra compacta neurons that innervate the reticular thalamic nucleus in the rat also project to striatum or globus pallidus: implications for abnormal motor behavior.

The projections of the substantia nigra pars compacta (SNc) to the reticular thalamic nucleus (RTn) were assessed by measuring dopamine content and counting tyrosine hydroxylase positive (TH (+)) cells in rats with unilateral lesions induced by 6-hydroxydopamine (6-OHDA), and by using a fluorescent tract-tracing technique in rats without lesions. Injection of 6-OHDA in the RTn reduced dopamine content and the number of TH (+) cells in the SNc by about 50%. Branching of SNc was suggested by the finding that 6-OHDA deposited in the RTn significantly reduced dopamine in the striatum and globus pallidus. Moreover, injections of 6-OHDA into either the striatum or the globus pallidus significantly reduced dopamine content in the RTn. Fluorescent tracers injected into the RTn labeled TH (+) cells in the SNc. A high proportion of these TH (+) cells was double labeled when tracers were also injected into either the globus pallidus or striatum. Other experiments showed that systemic injection of apomorphine or methamphetamine induced turning behavior in rats with local deposits of 6-OHDA in either the RTn or the studied basal ganglia nuclei. The extensive dopaminergic branching suggests that the abnormal motor behavior of rats with 6-OHDA deposits in the RTn may be caused by dopaminergic denervation of more than one structure. The fact that lesion of a single dopaminergic neuron can reduce dopamine transmission in more than one structure is probably important in generating the manifestations of Parkinson's disease.

Adrenergic Agents↗

PubMed1997

Activation of muscarinic receptors stimulates GABA release in the rat globus pallidus.

The effect of carbachol on the spontaneous release of 3H-GABA was investigated on rat globus pallidus (GP) slices. Carbachol dose-dependently enhanced the release of 3H-GABA. The carbachol (5 x 10(-4) M) induced 3H-GABA release is mediated by muscarinic receptors since atropine (10(-6) M), pirenzepine (10(-6) M) and AF-DX384MS (10(-6) M) abolished the effect. An indirect carbachol effect mediated by dopaminergic and glutamatergic afferents was ruled out since the effect was not blocked by either D1 (SCH23390 10(-6) M) and D2 (sulpiride 10(-5) M) receptor antagonists or by ionotropic glutamate receptor antagonists (CNQX 10(-6) M and 10(-5) M, MK801 10(-6) M). A direct effect is further evidenced by the persistence of the carbachol effect in the presence of tetrodotoxin (5 x 10(-7) M). Surprisingly the carbachol effect was not abolished by lowering the Ca2+ concentration of the superfusion medium or by increasing concomitantly the Mg2+ concentration. The involvement of a GABA transporter can partially explain this latter result, as nipecotic acid (10(-3) M) blocked the effect by only 50%. Carbachol stimulated the accumulation of 3H-phosphoinositides in pallidal slices, an effect that was antagonized by atropine (10(-6) M), pirenzepine (10(-6) M), and AF-DX384MS (10(-6) M). These results suggest that the activation of muscarinic receptors localized on striatopallidal terminals stimulates the release of GABA in the globus pallidus through inositol phosphate hydrolysis.

Animals↗

PubMed1984

A Golgi analysis of the primate globus pallidus. III. Spatial organization of the striato-pallidal complex.

An atlas of transverse sections of the globus pallidus and striatum was established in macaque with reference to ventricular coordinates. The three-dimensional geometry of the striato-pallidal complex was investigated by means of sagittal and horizontal reconstructions. Both a personal case studied with autoradiography and data from literature were used to analyze the distribution of cortical axons into the striatum. One may distinguish two striatal territories: one, somatotopically arranged, sensorimotor territory extending over the major part of the putamen; and the other, an associative territory, comprising the caudate nucleus and antero-medial and postero-inferior parts of the putamen. The striato-pallido-nigral bundle was studied using Golgi, Perls, and Fink-Heimer techniques. The bundle is described in four parts: prepallidal (subdivided into caudato-pallidal and putamino-pallidal subparts), transpallidal, pallido-nigral, and nigral. The tracing of the limit between the caudate (associative) and putaminal (essentially sensorimotor) territories shows that the two components are of roughly the same size in the pallidum. The data were compared with geometry and orientation of the dendritic arborizations of large pallidal neurons analyzed in Yelnik et al. ('84). Each pallidal dendritic disc is able to receive axons from a wide region of the striatum. This leads to a convergence on pallidal neurons of striatal axons from different striatal somatotopic strips and from the sensorimotor and associative territories. This is an indication that the globus pallidus may have an integrative role.

Animals↗

PubMed2003

Histological changes in neurons of the globus pallidus after experimental administration of dexamethasone.

The aim of our research was morphological assessment of neurons in the globus pallidus after 28-day administration of dexamethasone. The experiments were carried out on adult Albino Swiss mice males. It was found that prolonged administration of this glucocorticosteroid causes degenerative changes in neurons of the globus pallidus (shrinkage of nerve cells, increased stainability of nucleus and cytoplasm). We also observed increased numbers of glial cells in this area of the brain.

Animals↗

PubMed1994

High intensity in the globus pallidus on proton and T2-weighted MRI in a case of dentato-ruburo-pallido-luysian atrophy of myoclonus epilepsy type.

Although marked atrophy of the tegmentum of the mid-brain is a known computed tomography (CT) and magnetic resonance imaging (MRI) feature in patients with dentato-ruburo-pallido-luysian atrophy (DRPLA), this is the first report of marked high signal intensity of the globus pallidus on proton and T2-weighted MR images in a patient in the early stage of DRPLA of the myoclonus epilepsy type. We suggest that the globus pallidus may be involved in the early stage of DRPLA of this type. Magnetic resonance imaging is considered to be useful for the early detection of involvement of the globus pallidus and in the clinical diagnosis of DRPLA.

Adolescent↗

PubMed1999

Bilateral globus pallidus lesions in a patient with Tourette syndrome and related disorders.

BACKGROUND: The neuroanatomic and pathologic basis of Tourette's syndrome or related disorders such as obsessive-compulsive disorder and attention deficit-hyperactivity disorder remains unknown. Although a substantial body of neuroimaging and other data implicate basal ganglia and some point out specifically the globus pallidus in the etiopathogenesis of these three related disorders, no clear or pathologically significant isolated lesions restricted to this region have yet been demonstrated, with the exception of obsessive-compulsive disorder. METHODS: A seventeen-year-old male case of Tourette syndrome with comorbid obsessive-compulsive disorder, attention deficit-hyperactivity disorder, stuttering and gait disturbance, who had negative family history is presented. RESULTS: The patient has failed to respond to drug treatment and his MRI scan revealed bilateral and symmetrical globus pallidus lesions with specific "tiger's eye" appearance of unknown etiology. CONCLUSIONS: Well-localized lesions in the globus pallidus support growing data suggesting the involvement of this brain region in Tourette syndrome and related disorders.

Adolescent↗

PubMedDate not supplied

Echo-planar and gradient-echo diffusion MRI of normal brain iron in the globus pallidus.

The purpose of this study was to investigate effects of normal brain iron on proton diffusion and its quantification by diffusion MRI. The studies were undertaken in 24 cases ages ranging from 15 to 74 years (mean=45 years) with normal iron deposition in the globus pallidus to characterize the appearances on diffusion imaging with differing b values and on apparent diffusion coefficient (ADC) maps. Diffusion MRI was obtained by the spin-echo echo-planar imaging sequence (n=20 patients) or by the gradient-echo diffusion sequence, PSIF (n=4). In the PSIF sequence, pixel lens calculations were performed. In the echo-planar sequence, ADC value calculations were performed by using Stejskal-Tanner formula and by direct reading from automatically generated ADC maps. ADC values obtained from the normal appearing parenchyma were used as controls. Twenty patients with acute cerebral infarction were included for comparison of ADC values with those of iron deposition. The mean ADC value in the normal cerebral parenchyma was 0.85+/-0.11 x 10(-3) mm(2)/s. In the globus pallidus, mean ADC value was 48+/-0.12 x 10(-3) mm(2)/s. That of regions with acute infarction was 0.34+/-0.11 x 10(-3) mm(2)/s. On b=0 or 50, b=500 and b=1000 s/mm(2) images of the echo-planar diffusion imaging globus pallidus appeared hypointense compared to surrounding parenchymal structures. Low signal and low pixel values were evident on the PSIF imaging. This study indicates that, on diffusion MRI, normal iron deposition reveals prominent low signal on all the images of the echo-planar diffusion imaging sequence with differing b values, as well as on the gradient-echo diffusion, PSIF sequence. Low signal on ADC maps and low ADC values are evident. These represent characteristic diffusion MRI features of normal iron deposition in the brain, reflecting susceptibility effects.

Brain↗

PubMed1994

Unusual ubiquitin-positive glial cells in the globus pallidus of normal elderly human brains.

Unusual glial cells, inconspicuous in routine histological sections, were demonstrated in the globus pallidus using immunohistochemistry for anti-ubiquitin and a modified NOR-silver impregnation technique. These cells were identified as astrocytes and showed the following unusual features: (i) presence of intracytoplasmic vacuoles; (ii) immunoreactivity for ubiquitin; (iii) positive staining with a modified NOR-silver impregnation technique; and (iv) topographical location restricted to the globus pallidus. Quantitative analyses showed the numerical density of these cells to be significantly increased with normal ageing, whereas the presence of the cells was not related to pathological ageing or any other disease process. The data suggest that, not only in neurons but also in glial cells, accumulations of altered proteins can be found, which is probably due to a decline in the proteolytic activity of the cell.

Adult↗

PubMed2002

Globus pallidus glial pigment and its changes with age and chronic illness in childhood.

Glial lipopigment appears in the globus pallidus without accumulating in neurons (except for late adolescence) in multiple chronic childhood diseases. In this observational study, we compared the age-related development of glial pigmentation in children with the chronic illness (cystic fibrosis) and children dying acutely. A secondary goal was to search for pallidal neuronal lipopigment in childhood. We recorded pigmentation in the brains of 37 consecutive cystic fibrosis children ranging in age from 0-23 yr and in 17 controls ranging in age from 0-18 yr. We characterized the lipofuscin histochemically and used several regression models to describe the mode of deposition. We observed that in the controls, intraglial pallidal pigment accumulated in 2 forms (relatively large globules and, separately, as clusters of fine granules) at a slow rate during childhood. In cystic fibrosis, both forms of pallidal glial pigment started accumulating at a younger age and were deposited far more rapidly. There was a further increase in the rate of accumulation between 8 and 10 yr of age. We did not encounter pallidal neuronal lipofuscin at any age. These observations are consistent with 2 propositions: 1) that globus pallidus glial cells are unique in their ability to accumulate lipofuscin before it accumulates in nearby neurons; and 2) that they are particularly susceptible to some systemic effect of this chronic illness.

Adolescent↗