Apomorphine increases the activity of rat globus pallidus neurons

Systemic administration of apomorphine, 0.08–1.0 mg/kg, caused a haloperidol-reversible increase in the unit activity of spontaneously firing neurons in the rat globus pallidus. Low doses of apomorphine (50, 20 μg/kg), which are thought to produce a net decrease in the stimulation of postsynaptic dopamine receptors, did not cause effects opposite to those observed with larger doses in 96% of the cells monitored. Blockade of dopamine receptors by administration of haloperidol did cause a moderate reduction in neuronal activity but only after administration of fairly high doses.     

Stimulation of the globus pallidus internus for childhood-onset dystonia.

We report the results of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in 12 patients with childhood-onset generalized dystonia refractory to medication, including 3 patients with status dystonicus. There were 8 patients who had DYT1-negative primary dystonia, 1 had DYT1-positive dystonia, and 3 had symptomatic dystonia. Stimulation was effective in all but 1 patient. Dystonic postures and movements of the axis and limbs responded to DBS to a greater extent than oromandibular dystonia and fixed dystonic postures. These findings provide further evidence that pallidal stimulation is an effective treatment for intractable childhood-onset dystonia, including status dystonicus, and together with previous findings, suggest that it should be considered the treatment of choice for these conditions.     

Projections of the feline globus pallidus

The organization of globus pallidus (GP) projections was studied in cats using autoradiographic and horseradish peroxidase (HRP) techniques. Both methods confirmed the existence of a topographically organized projection to subthalamic nucleus (STN). Although all but the most caudal GP projects to STN, the heaviest projection is to the lateral two-thirds. In addition, HRP studies showed that the GP projection to the medial part of substantia nigra, pars reticulata receives projections from the rostral lateral GP, while lateral substantia nigra receives input from caudal GP. There is in addition a small projection from caudal GP to the caudal lateral mesencephalon. This most caudal projection of GP arises from the portion of GP which projects the least to the subthalamic nucleus. Mesencephalic and pontine cells labeled after injection of horseradish peroxidase into STN were in areas receiving projections from GP and entopeduncular nucleus, suggesting there may be reciprocal relationships between these areas. Labeled cells were located in the lateral part of subthalamic nucleus after injection into the lateral portion of substantia nigra pars reticulata, but cells were not labeled after medial injection. Pontine injections of HRP also revealed that cells in fields of Forel and zona incerta project to pons but very few subthalamic nucleus cells project there.     

Local field potentials and oscillatory activity of the internal globus pallidus in myoclonus-dystonia.

The pathophysiology of myoclonus-dystonia (M-D), an autosomal dominantly inherited movement disorder characterized by myoclonic jerks and dystonic contractions, is largely unknown. In the present study, local field potential (LFP) activities in the globus pallidus internus (GPi) from two genetically proven M-D patients are investigated. Coherence analysis between GPi LFP activity and electromyographic muscle activity (EMG) and synchronization of GPi neuronal activity using event-related spectral perturbation (ERSP) in a go-no-go paradigm were studied. Significant increased coherence in the 3 to 15 Hz frequency band was detected between GPi LFP activity and several muscles, with the LFP leading the muscles. The ERSP analysis revealed synchronization in the 3 to 15 Hz frequency band within the GPi before the imperative cue of the go-no-go task and desynchronization in the same band after the cue. The LFP recordings of the GPi in M-D show that the low-frequency band previously described in dystonia is also involved in the dystonia plus syndrome M-D. The 3 to 15 Hz synchronization in the go-no-go paradigm has not been described previously and may point to the existence of (myoclonus-)dystonia specific oscillatory activity in the GPi.     

Acute stimulation in the external segment of the globus pallidus improves parkinsonian motor signs.

High frequency (>100Hz) electrical stimulation in both the external (GPe) and internal (GPi) segments of the globus pallidus was effective in improving parkinsonian motor signs. Improvement generally occurred at short latency (<5-10 seconds) in both GPe and GPi but was often (50% of the time) delayed in GPi. Dyskinetic movements were observed during stimulation within GPe and GPi but were more frequent in GPe (20% vs. 9%). These findings suggest that electrical stimulation in both GPe and GPi may ameliorate parkinsonian motor signs. The mechanisms responsible for these observations, however, may differ. The tendency for delayed responses with GPi stimulation suggests a more complex spatial-temporal profile of stimulation on the electrical activity of GPi neurons and/or its effect on network activity in pallido-thalamo-cortical circuitry. The rarity of delayed effects with GPe stimulation suggests a more direct role of synaptic inhibition or normalization of neuronal activity of GPi either directly by means of activation of striatopallidal fibers passing through GPe (direct pathway), by means of activation of GPe-->GPi or GPe-->subthalamic nucleus projections (indirect pathway) or indirectly by means of the tonic activation of adjacent fiber pathways. These data provide a rationale for the exploration of electrical stimulation in GPe in patients with medically intractable Parkinson's disease and provide a basis on which to develop further investigations into the use of chronic electrical stimulation for the treatment of Parkinson's disease and other movement disorders.     

Unilateral deep brain stimulation of the internal globus pallidus alleviates tardive dyskinesia.

We describe a patient with fluspirilene-induced tardive dyskinesia of the choreiform oro-facial-laryngeal type resistant to various conservative approaches for 7 years who underwent deep brain stimulation of the internal pallidal globe. We found immediate and marked suppression of her perioral involuntary movements with unilateral stimulation at 60 Hz.     

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.     

Chorea induced by globus pallidus externus stimulation in a dystonic patient.

Bilateral high-frequency stimulation of the internal part of the pallidum has proven its efficacy in improving motor symptoms of dystonia. In Parkinson's disease, the stimulation of the external pallidum (GPe) can induce dyskinesias. This has never been described in dystonia. We report here a case of abnormal movements induced by the stimulation of GPe in a dystonic patient and discuss the pathophysiological mechanisms.     

Interruption of deep brain stimulation of the globus pallidus in primary generalized dystonia

Stimulation (DBS) of the globus pallidus (GP) is effective to treat generalized dystonia. Little is known about the evolution of dystonia in case of arrest after a long period of stimulation. This study describes the course of dystonia during a 48 hours period without stimulation followed by a 24 hours period after turning ON the stimulator. 14 patients with generalized dystonia treated with bilateral GP DBS for 3 years or more were recruited. Blinded video‐based analysis was performed using Burke‐Fahn‐Marsden scale at (1) baseline (ON stimulation), (2) up to 48 hours after the stimulator was turned OFF, and (3) 24 hours after the stimulator was turned ON. 13 patients completed the 48 hours OFF‐stimulation period. The dystonia movement score progressively worsened from 24.3 ± 13.9 at baseline to 48.9 ± 19.8 after 48 hours (P < 0.00001). The disability score also worsened from 4.4 ± 1.2 at baseline to 5.7 ± 1.5 after 48 hours without stimulation (P < 0.001). When the neurostimulator was turned ON, the dystonia scores returned to baseline level after 10 hours. The interruption of GP DBS in dystonia results in a progressive worsening which is rapidly reversible once the neurostimulator is turned ON. © 2009 Movement Disorder Society     

Long-term follow-up of globus pallidus chronic stimulation in advanced Parkinson's disease.

To assess the long-term follow-up of the globus pallidus internus (GPi) stimulation, six patients were evaluated every year by using the Unified Parkinson's Disease Rating Scale (UPDRS). Three years postoperatively, GPi stimulation led to a significant improvement of dyskinesia severity (50%, P = 0.05) and activities of daily living (subscore of quality of life scale, 9%, P = 0.05). However, the improvement induced by chronic pallidal stimulation on the mean daily duration in the off state was lost at the last assessment.     

Behaviorally specific limb use deficits following globus pallidus lesions in rats

The effects of bilateral globus pallidus lesions were observed in rats trained to perform a somatosensory/proprioceptive guided forelimb reaching task. Postlesion reaching became very inaccurate, characterized by gross abnormalities in limb and body posture. Postural abnormalities and paw use deficits were not observed in other situations. These results suggest that pallidal damage does not result in a simple motor deficit but interferes with motor performance when movements depend upon somesthetic and proprioceptive feedback.     

Bilateral deep brain stimulation of the globus pallidus internus in tardive dystonia

Tardive dystonia is a disabling movement disorder as a consequence of exposure to neuroleptic drugs. We followed 6 patients with medically refractory tardive dystonia treated by bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for 21 ± 18 months. At last follow‐up, the Burke‐Fahn‐Marsden Dystonia Rating Scale (BFMDRS) motor score improved by 86% ± 14%, and the BFMDRS disability score improved by 80% ± 12%. Bilateral GPi‐DBS is a beneficial therapeutic option for the long‐term relief of tardive dystonia. © 2008 Movement Disorder Society     

Influence of nitric oxide on the spontaneous activity of globus pallidus neurones in the rat

Summary. Previous observations have suggested a role for nitric oxide in the activity of the globus pallidus, but this functional involvement has not yet been tested in vivo. The extracellular activity of single units of the globus pallidus was recorded, and neuronal nitric oxide synthase was inhibited by systemically administering 7-nitro-indazole to a group of anaesthetised rats. Forty-five per cent of cells responded with a decrease in the firing rate. In another group of rats, the microiontophoretic administration of 3-morpholino-sydnonimin-hydrocloride (a nitric oxide donor) induced an increase in neuronal firing rate (24/28 cells), whereas the administration of Nω-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) reduced the activity of pallidal neurones (8/11 cells). No electrophysiological differences between drug-sensitive and -insensitive neurones were evidenced. An excitatory role of nitric oxide in controlling the level of spontaneous activity of globus pallidus neurones is suggested, without any influence upon the discharge pattern. Received February 4, 2002; accepted March 6, 2002 Published online June 28, 2002 Acknowledgements This work was supported by grants from the Consiglio Nazionale delle Ricerche and the Ministero dell'Università e della Ricerca Scientifica e Tecnologica, Roma, Italy. Authors' address: Prof. V. La Grutta, Dipartimento di Medicina Sperimentale – Sezione di Fisiologia umana, Università degli Studi di Palermo, Corso Tukory, 129, I-90134 Palermo, Italy, e-mail: vlgfisio@unipa.it     

Tonic and phasic changes in anteromedial globus pallidus activity in Tourette syndrome

Background : Tourette syndrome is a hyperkinetic neurodevelopmental disorder characterized by tics. Objective : Assess the neuronal changes in the associative/limbic GP associated with Tourette syndrome. Methods : Neurophysiological recordings were performed from the anterior (associative/limbic) GPe and GPi of 8 awake patients during DBS electrode implantation surgeries. Results : The baseline firing rate of the neurons was low in a state‐dependent manner in both segments of the GP. Tic‐dependent transient rate changes were found in the activity of individual neurons of both segments around the time of the tic. Neither oscillatory activity of individual neurons nor correlations in their interactions were observed. Conclusions : The results demonstrate the involvement of the associative/limbic pathway in the underlying pathophysiology of Tourette syndrome and point to tonic and phasic modulations of basal ganglia output as a key mechanisms underlying the abnormal state of the disorder and the expression of individual tics, respectively. © 2017 International Parkinson and Movement Disorder Society     

Complete suppression of paroxysmal nonkinesigenic dyskinesia by globus pallidus internus pallidal stimulation.

Stereotactic functional surgery is being explored as potential therapies for medically intractable paroxysmal dyskinesias (PxD). We report on a 59-year-old man in whom stimulation of globus pallidus internus produced immediate and sustained relief of paroxysmal non-kinesigenic dyskinesia secondary to a rotator cuff tears on the left shoulder. Our finding strongly suggests that altered function of neuronal circuits of the basal ganglia underlies the manifestation of PxD.     

Role of postural deficits in oro-ingestive problems caused by globus pallidus lesions

There is a large literature demonstrating that rats with globus pallidus lesions have ingestional problems. In an effort to understand the bases of these deficits, the ingestional activity of normal and brain-damaged animals was subjected to scrutiny. Rats were trained to lick a spout recessed behind a Plexiglas wall for 8% sucrose solution. The characteristic interlick interval and lick duration distributions observed in normal animals were severely disrupted by globus pallidus lesions. This disturbance was, in large part, due to an inability to correctly position the mouth with respect to the spout and maintain that position for a burst of licks, activities which normally ensure consistently efficient ingestion. After pallidal lesions, animals often miss the spout altogether. When they do find the spout, only the first few licks are on target. The head then drifts away from the correct position and subsequent licks miss the spout. Animals' ability to continue licking during slow lateral displacement of the spout was also tested. Animals with pallidal lesions showed severe deficits. In addition to problems with head positioning, pallidal animals failed to adapt their body posture to enable licking at different spout locations. In relation to clinical and experimental findings, these data implicate the basal ganglia in feedback-regulated control of axial and proximal muscles.     

Bilateral globus pallidus internus deep brain stimulation in tardive dyskinesia: a case report.

The clinical response of a 53-year-old woman with tardive dyskinesia treated with bilateral globus pallidus interna deep brain stimulation is described. At 18 months follow-up, her Burke-Fahn-Marsden Dystonia Rating Scale score fell from 52 (preoperative) to 21 (60% improvement).     

苍白球在电针镇痛及兴奋尾壳核镇痛中的作用

用行为学和电生理学的方法 ,探讨苍白球在电针镇痛及兴奋尾壳核镇痛中的作用。结果表明 :电针可以延长辐射热引起的缩腿潜伏期 ,电针或兴奋尾壳核可抑制丘脑束旁核神经元的伤害性反应 ;苍白球微量注射红藻氨酸 7d后 ,电针对辐射热引起的大鼠缩腿潜伏期无明显影响 ,电针或兴奋尾壳核对丘脑束旁核神经元的伤害性反应亦无明显影响 ,与毁损前相比有显著性差异 (P <0 .0 5 ) ,与苍白球微量注射生理盐水 7d后 ,电针可延长大鼠缩腿潜伏期 ,及电针或兴奋尾壳核对束旁核神经元伤害性反应的抑制作用相比有显著性差异 (P <0 .0 5 )。结果提示 :苍白球在电针及兴奋尾壳核镇痛中发挥重要作用     

Distinct changes in evoked and resting globus pallidus activity in early and late Parkinson's disease experimental models

The main clinical manifestations of Parkinson's disease are caused by alterations of basal ganglia activity that are tied in with the progressive loss of mesencephalic dopaminergic neurons. Recent theoretical and modeling studies have suggested that changes in resting neuronal activity occurred later in the course of the disease than those evoked by phasic cortical input. However, there is no empirical support for this proposal. Here we report a marked increase in the responsiveness of globus pallidus neurons to electrical motor cortex stimulation, in the absence of noticeable changes in resting activity, in anesthetized rats that had consistently shown a deficit in forelimb use during behavioral testing before the experiments, and had approximately 45% dopamine neurons spared in the substantia nigra. Pallidal neurons were also over-responsive to motor cortex stimulation and lost spatial selectivity for cortical inputs in rats with extensive nigrostriatal damage. After partial lesions, over-responsiveness was mainly due to an increased proportion of neurons showing excitatory responses, while extensive lesions led to an increased likelihood of inhibitory responding neurons. Changes in resting neuronal activity, comprising pauses disrupting tonic discharge, occurred across different global brain states, including an activated condition which shares similarities with natural patterns of cortical activity seen in awake states and rapid eye-movement sleep, but only after massive nigrostriatal degeneration. These results suggest that a loss of functional segregation and an abnormal temporal encoding of phasic cortical inputs by globus pallidus neurons may contribute to inducing early motor impairment in Parkinson's disease.     

A Golgi analysis of the primate globus pallidus. I. Inconstant processes of large neurons, other neuronal types, and afferent axons

The present paper is a Golgi study, with high-power lenses, of the primate globus pallidus. Two kinds of inconstant processes of large neurons are first described: complex endings and thin processes. Complex endings are thick apparatuses terminally located on dendrites having many appendages of various types. Contacts were observed not only between striatal axons and these complex endings but also between complex endings and the soma, dendritic stems, dendritic portions or complex endings of other large pallidal neurons. Thin processes were usually beaded, very thin, and arose from any part of the dendritic tree. Contacts were seen between them and soma or dendrites of other large neurons. These thin processes were very similar to initial axonal collaterals and together constitute a common pool of processes. Complex endings and thin processes were essentially observed in the lateral nucleus of the pallidum where they apparently are evenly distributed inside the nucleus but randomly distributed on individual neurons. Two neuronal types other than large pallidal neurons were isolated: the smallest were considered to be local circuit neurons, while intermediate-sized neurons might be the origin of a particular efference. Many striatal axons gave no branches over long distances and collaterals were of two types and most frequently were short (less than 50 micron). Larger axonal arborization were rarely encountered. In addition to parallel contacts, numerous very short ones were observed. All these contacts between striatal axons and dendrites of large pallidal neurons seem to be irregularly distributed.