Disinhibition as a basic process in the expression of striatal functions. II. The striato-nigral influence on thalamocortical cells of the ventromedial thalamic nucleus

Deniau, Jean-Michel; Chevalier, G.

doi:10.1016/0006-8993(85)90214-8

Cited by 287 publications

(143 citation statements)

References 28 publications

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“…We have proposed that increased, regularized GPi activity during DBS of STN actually allows for normal thalamic responses, because the resulting tonic inhibition to TC cells does not induce the low-thresold calcium rebound bursts that we observe in the parkinsonian state (and which have been observed experimentally to result from pauses in high-frequency SNr firing, Deniau and Chevalier, 1985). Previous authors have also suggested that DBS of STN disrupts pathological patterns or over-synchronization of GPi activity (Ryan et al, 1993;Obeso et al, 1997;Montgomery and Baker, 2000;Obeso et al, 2000;Vitek et al, 2000Vitek et al, , 2002Benabid et al, 2001c).…”

Section: Discussionmentioning

confidence: 80%

High Frequency Stimulation of the Subthalamic Nucleus Eliminates Pathological Thalamic Rhythmicity in a Computational Model

2004

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Abstract. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) has recently been recognized as an important form of intervention for alleviating motor symptoms associated with Parkinson's disease, but the mechanism underlying its effectiveness remains unknown. Using a computational model, this paper considers the hypothesis that DBS works by replacing pathologically rhythmic basal ganglia output with tonic, high frequency firing. In our simulations of parkinsonian conditions, rhythmic inhibition from GPi to the thalamus compromises the ability of thalamocortical relay (TC) cells to respond to depolarizing inputs, such as sensorimotor signals. High frequency stimulation of STN regularizes GPi firing, and this restores TC responsiveness, despite the increased frequency and amplitude of GPi inhibition to thalamus that result. We provide a mathematical phase plane analysis of the mechanisms that determine TC relay capabilities in normal, parkinsonian, and DBS states in a reduced model. This analysis highlights the differences in deinactivation of the low-threshold calcium T -current that we observe in TC cells in these different conditions. Alternative scenarios involving convergence of thalamic signals in the cortex are also discussed, and predictions associated with these results, including the occurrence of rhythmic rebound bursts in certain TC cells in parkinsonian states and their drastic reduction by DBS, are stated. These results demonstrate how DBS could work by increasing firing rates of target cells, rather than shutting them down.

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Section: Discussionmentioning

confidence: 80%

High Frequency Stimulation of the Subthalamic Nucleus Eliminates Pathological Thalamic Rhythmicity in a Computational Model

2004

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“…The basal ganglia motor circuit is thus viewed as holding the thalamic and brainstem networks in check [13][14][15][16], and the level of tonic and phasic inhibition is determined by the interplay of direct, indirect, and hyperdirect pathways at the level of GPi/SNr.…”

Section: Functional/anatomic Considerations Of the Basal Ganglia Circmentioning

confidence: 99%

“…Metabolic studies suggested [140,141], and microelectrode recording studies demonstrated, a reduction of neuronal discharge in GPe, and increased activity in the STN, leading to increased excitatory drive upon the basal ganglia output nuclei, GPi, and SNr [142][143][144][145], all strongly implicating increased activity over the indirect pathway in the pathophysiology of PD. Based on this evidence, models were developed positing that akinesia/bradykinesia results from excessive inhibitory output from GPi [13,15,16], and emphasizing the role of increased GPi output in hypokinetic and decreased output in hyperkinetic disorders.…”

Section: Pathophysiology Of Parkinsonism and Dystoniamentioning

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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“…Though it has been appreciated for some time that disinhibition is the major mechanism for signaling among GABAergic neurons in the basal ganglia (e.g., Chevalier et al, 1985;Deniau and Chevalier, 1985;Chevalier and Deniau, 1990), it is only more recently that this mode of control has been shown to apply to the nigrostriatal neurons as well. A crucial first step in understanding the neuronal interactions that control the activity of nigral dopaminergic neurons was the discovery that nigral GABAergic projection neurons strongly inhibit the dopaminergic neurons through their axon collaterals.…”

Section: Discussionmentioning

confidence: 99%

Pallidal control of substantia nigra dopaminergic neuron firing pattern and its relation to extracellular neostriatal dopamine levels

2004

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Disinhibition as a basic process in the expression of striatal functions. II. The striato-nigral influence on thalamocortical cells of the ventromedial thalamic nucleus

Cited by 287 publications

References 28 publications

High Frequency Stimulation of the Subthalamic Nucleus Eliminates Pathological Thalamic Rhythmicity in a Computational Model

High Frequency Stimulation of the Subthalamic Nucleus Eliminates Pathological Thalamic Rhythmicity in a Computational Model

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

Pallidal control of substantia nigra dopaminergic neuron firing pattern and its relation to extracellular neostriatal dopamine levels

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