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

Heimer, Gali; Bar‐Gad, Izhar; Goldberg, Joshua A.; Bergman, Hagai

doi:10.1523/jneurosci.22-18-07850.2002

Cited by 161 publications

(152 citation statements)

References 32 publications

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“…Our previous studies of simultaneously recorded cells indicated that, in the normal monkey, the activity of pallidal neurons is uncorrelated (Nini et al, 1995;Heimer et al, 2002). These results were presented as supporting the hypothesis of the parallel (vs funneling) organization of the basal ganglia circuitry (Bergman et al, 1998).…”

Section: Introductionsupporting

confidence: 65%

“…2). However, these cross-correlograms are very different from the flat crosscorrelograms typical of pallidal pairs recorded by different electrodes (Nini et al, 1995;Heimer et al, 2002). The correlation of neighboring neurons has multiple stereotypic phases: a decreased correlation around time 0 followed by an increase to higher than mean correlations on the time scale of the refractory period of the cells.…”

Section: Autocorrelations and Cross-correlations Of Pallidal Neuronsmentioning

confidence: 78%

“…After training, a Cilux recording chamber was attached to the skull to allow recording of the activity of pallidal neurons. Details of the task, surgery, and data-recording methods are similar to those given previously (Nini et al, 1995;Heimer et al, 2002). The care of the monkeys and surgical procedures were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (1996) and with the Hebrew University guidelines for the use and care of laboratory animals in research, and were supervised by the Institutional Animal Care and Use Committee.…”

Section: Methodsmentioning

confidence: 99%

“…Only pairs that satisfied the inclusion criteria for at least 600 sec were included in the analysis. Autocorrelation and cross-correlation functions were normalized to firing rate (Nini et al, 1995;Heimer et al, 2002), and no smoothing was applied.…”

Section: Methodsmentioning

confidence: 99%

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Functional Correlations between Neighboring Neurons in the Primate Globus Pallidus Are Weak or Nonexistent

Bar‐Gad¹,

Heimer²,

Ritov³

et al. 2003

J. Neurosci.

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The anatomical structure of the basal ganglia displays topographical organization and massive funneling of neuronal projections toward the globus pallidus as well as an axonal collateral system within this nucleus. This structure suggests the formation of correlations between the spiking activities of pallidal cells. Nevertheless, previous studies of remote neurons in the pallidum have reported uncorrelated spiking activity. These correlation results may be challenged, because remote pallidal neurons may be located in different pallidal territories. To further test the independence of pallidal activity, we studied the spiking activity of neighboring pairs recorded by the same electrodes. A narrow peak dominated the correlations of all pairs of neurons recorded on the same electrode. This type of peak is classically interpreted as a sign of strong common input. However, recent mathematical analysis shows that such peaks may derive from a technical inability to detect overlapping spikes by spike-sorting techniques. A long-term shallow trough in the correlation of neighboring neurons may also result from the same effect, which we have termed the "shadowing effect." A comparison of the expected shadowing effect with the actual correlations suggests that no real correlations exist between 93.9% of neighboring pallidal pairs. The remaining 6.1% of the pairs display symmetric long-term positive correlations centered on time 0. Thus, functional interactions between neighboring pallidal neurons donotdisplayanysignificantdifferencesfromtheinteractionsbetweenphysicallyremoteneuronsinthisbrainarea.Moreover,thecombination of anatomical data and current physiological results suggests an active decorrelating process performed in the basal ganglia.

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Section: Introductionsupporting

confidence: 65%

Section: Autocorrelations and Cross-correlations Of Pallidal Neuronsmentioning

confidence: 78%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Functional Correlations between Neighboring Neurons in the Primate Globus Pallidus Are Weak or Nonexistent

Bar‐Gad¹,

Heimer²,

Ritov³

et al. 2003

J. Neurosci.

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“…The finding of increased cross-correlation of single-cell discharge in many basal ganglia regions in animal models and patients with PD and increased LFP amplitudes in specific power spectral ranges indicates that the normal level of independence of discharge is substantially reduced in the parkinsonian state [44,322,323,325,326]. Effective antiparkinsonian therapies, including levodopa replacement and DBS reduce the LFP amplitudes to more normal levels, and reduce the abnormal synchrony of neurons in at least some brain regions [see, e.g., 152,297,327].…”

Section: Abnormal Levels Of Synchrony May Be a Fundamental Electrophymentioning

confidence: 99%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

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Deep brain stimulation (DBS) is highly effective for both hypo-and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal gangliathalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

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Motor Pathways, Basal Ganglia Physiology, and Pathophysiology

Bergman¹,

Katabi²,

Slovik³

et al. 2015

Brain Stimulation

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

Cited by 161 publications

References 32 publications

Functional Correlations between Neighboring Neurons in the Primate Globus Pallidus Are Weak or Nonexistent

Functional Correlations between Neighboring Neurons in the Primate Globus Pallidus Are Weak or Nonexistent

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

Motor Pathways, Basal Ganglia Physiology, and Pathophysiology

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