Apomorphine induces changes in GPi spontaneous outflow in patients with parkinson's disease

Merello, Marcelo; Balej, Jorge; Delfino, Marina; Cammarota, Angel; Betti, Osvaldo; Leiguarda, R.

doi:10.1002/1531-8257(199901)14:1<45::aid-mds1009>3.3.co;2-6

Cited by 12 publications

(15 citation statements)

References 7 publications

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“…Interestingly, an increased irregularity of spontaneous firing was also indicated by intrasurgical recordings of GPi neurons in patients with generalized dystonia when compared with patients suffering from idiopathic Parkinson's disease (Vitek et al, 1999). Additionally, a change in the pattern of GPi neurons was reported for Parkinson's disease patients developing drug-induced dyskinesias (Merello et al, 1999).…”

Section: Discussionmentioning

confidence: 88%

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Altered Discharge Pattern of Basal Ganglia Output Neurons in an Animal Model of Idiopathic Dystonia

Gernert¹,

Bennay²,

Fedrowitz³

et al. 2002

J. Neurosci.

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A decreased activity of basal ganglia output neurons is thought to underlie idiopathic dystonias and other hyperkinetic movement disorders. We found recently a reduced spontaneous discharge rate of entopeduncular neurons (internal globus pallidus in primates) in dt(sz) hamsters, an unique model for idiopathic paroxysmal dystonia in which stress-inducible attacks show an age-dependent severity. Otherwise, it has been suggested that an altered discharge pattern may be more important for the occurrence of dystonia than a reduced discharge rate. Based on qualitative and computerized quantitative evaluations of interspike interval histograms and spike trains of extracellularly recorded single neurons, we investigated the spontaneous discharge pattern of GABAergic entopeduncular and nigral neurons in dt(sz) hamsters at different ages. The discharge pattern of entopeduncular neurons was highly irregular and showed an altered burst-like firing in dt(sz) hamsters at the age of the most marked expression of dystonia when compared with age-matched nondystonic controls. In line with a recently reported normalization of discharge rates after age-dependent disappearance of dystonia, we found an almost complete normalization of the discharge pattern of entopeduncular neurons after remission of dystonia in dt(sz) hamsters. Investigations of GABAergic nigral neurons, reported recently to have the same spontaneous discharge rates in dystonic and nondystonic hamsters, did not show an altered firing pattern in dt(sz) hamsters. The present data clearly indicate the fundamental importance of an altered discharge pattern of entopeduncular neurons for the expression of paroxysmal dystonia, and probably also for other dyskinesias, and may explain the improvements obtained by pallidotomy in dystonic patients despite an obviously reduced pallidal output.

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Section: Discussionmentioning

confidence: 88%

“…put activity is hypothesized (Mitchell et al, 1990;Wichmann and DeLong, 1996;Suarez et al, 1997;Berardelli et al, 1998;Crossman and Brotchie, 1998;Hallett, 1998;Merello et al, 1999;Filion, 2000;Vitek and Giroux, 2000).…”

mentioning

confidence: 99%

Altered Discharge Pattern of Basal Ganglia Output Neurons in an Animal Model of Idiopathic Dystonia

Gernert¹,

Bennay²,

Fedrowitz³

et al. 2002

J. Neurosci.

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“…The normal GPi firing rate in primates is in the range 60-90 s −1 , with an increase of about 10-20 s −1 after MPTP treatment in monkeys (Filion and Tremblay, 1991;Heimer et al, 2002;Yoshida, 1991). In line with these results, normalization of dopamine levels by application of the dopamine agonist apomorphine decreases the average firing rate of GPi neurons in PD patients (Merello et al, 1999). On the other hand, some studies found no significant change in average firing rates of GPi (Bergman et al, 1994;Wichmann et al, 1999) or its rodent homolog, the entopeduncular nucleus (EP) (Robledo and Feger, 1991).…”

Section: Data On Firing Rates In Normal and Parkinsonian Statesmentioning

confidence: 82%

Mean-field modeling of the basal ganglia-thalamocortical system. I

Albada¹,

Robinson²

2009

Journal of Theoretical Biology

155

161

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Parkinsonism leads to various electrophysiological changes in the basal ganglia-thalamocortical system (BGTCS), often including elevated discharge rates of the subthalamic nucleus (STN) and the output nuclei, and reduced activity of the globus pallidus external segment (GPe). These rate changes have been explained qualitatively in terms of the direct/indirect pathway model, involving projections of distinct striatal populations to the output nuclei and GPe. Although these populations partly overlap, evidence suggests dopamine depletion differentially affects cortico-striato-pallidal connection strengths to the two pallidal segments. Dopamine loss may also decrease the striatal signal-to-noise ratio, reducing both corticostriatal coupling and striatal firing thresholds. Additionally, nigrostriatal degeneration may cause secondary changes including weakened lateral inhibition in the GPe, and mesocortical dopamine loss may decrease intracortical excitation and especially inhibition. Here a meanfield model of the BGTCS is presented with structure and parameter estimates closely based on physiology and anatomy. Changes in model rates due to the possible effects of dopamine loss listed above are compared with experiment. Our results suggest that a stronger indirect pathway, possibly combined with a weakened direct pathway, is compatible with empirical evidence. However, altered corticostriatal connection strengths are probably not solely responsible for substantially increased STN activity often found. A lower STN firing threshold, weaker intracortical inhibition, and stronger striato-GPe inhibition help explain the relatively large increase in STN rate. Reduced GPe-GPe inhibition and a lower GPe firing threshold can account for the comparatively small decrease in GPe rate frequently observed. Changes in cortex, GPe, and STN help normalize the cortical rate, also in accord with experiments. The model integrates the basal ganglia into a unified framework along with an existing thalamocortical model that already accounts for a wide range of electrophysiological phenomena. A companion paper discusses the dynamics and oscillations of this combined system.

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“…Firing rates of the internal segment of the GP (GP i ) cells are increased, whereas the external segment of the GP (GP e ) cells display decreased firing rates (Miller and DeLong, 1987;. Single-electrode recordings performed on human parkinsonian patients during surgical interventions designed to relieve parkinsonian symptoms indicate trends in firing rates similar to those found in primates (Hutchison et al, 1994;Merello et al, 1999).…”

mentioning

confidence: 91%

“…Many electrophysiological studies have indicated that the changes of pallidal firing rates are reversed after administration of dopamine replacement therapy (DRT) in humans (Hutchinson et al, 1997;Merello et al, 1999;Levy et al, 2001) and primates Papa et al, 1999) (but see Boraud et al, 1998). However, all of these studies were confined to the activity of single neurons.…”

mentioning

confidence: 99%

Dopamine Replacement Therapy Reverses Abnormal Synchronization of Pallidal Neurons in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Primate Model of Parkinsonism

et al. 2002

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Previous physiological studies have revealed changes in firing rates and synchronization of pallidal neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson's disease. Several primate and human studies have demonstrated that dopamine replacement therapy (DRT) reverses the changes in the pallidal firing rates; however, the effects of DRT on pallidal synchronization have never been explored. To do so, we recorded the simultaneous activity of pallidal neurons of a vervet monkey before and after induction of severe parkinsonism by systemic MPTP treatment. We subsequently recorded the pallidal activity before and after daily administration of oral DRT. We extended the time scale of our correlation studies to +/-5 sec to allow detection of long-duration synchronized neuronal activity. After MPTP treatment, firing rates decreased in the external segment of the globus pallidus (GP(e)) and increased in the internal segment (GP(i)). A reversal of these rate changes occurred during the "on" periods of DRT. The percentage of correlated pairs increased from 16.7% in the normal state to 46.9% after MPTP treatment and was restored to nearly normal values (25% correlated pairs) under the influence of DRT. These changes in rate and correlation were observed at both the population level and at the level of units recorded continuously before, during, and after the clinical transition from "off" to "on" periods. We conclude that changes in both pallidal discharge rates and synchronization are correlated with the clinical manifestations of parkinsonism and its pharmacological treatment.

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Apomorphine induces changes in GPi spontaneous outflow in patients with parkinson's disease

Cited by 12 publications

References 7 publications

Altered Discharge Pattern of Basal Ganglia Output Neurons in an Animal Model of Idiopathic Dystonia

Altered Discharge Pattern of Basal Ganglia Output Neurons in an Animal Model of Idiopathic Dystonia

Mean-field modeling of the basal ganglia-thalamocortical system. I

Dopamine Replacement Therapy Reverses Abnormal Synchronization of Pallidal Neurons in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Primate Model of Parkinsonism

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