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Abstract Details

Striatal Cholinergic Agonist Infusion Induces a Dystonic Phenotype in Non-human Primate
Movement Disorders
S26 - Movement Disorders: Basic Science (5:18 PM-5:30 PM)

Dystonia is a debilitating motor disorder of unclear pathophysiology without specific pharmacological treatment. So far, novert phenotype of dystonia was obtained in rodent genetic-based models but a line of evidence suggested a potential dysregulation of the intra-striatal cholinergic system.



In this work, we aimed at engineering an original model of dystonia in the non-human primates(NHPsby increasing the cholinergic tone in the sensory-motor striatum.

This study was performed on 2 sub-human primates (Macaca Mulata). Two intracerebral canulas were implanted in the motor part of the striatum of each primate. NaCl- was delivered during control condition and Oxotremorin- M (Tocris Bioscience, UK), a non specific cholinergic agonist was used to induce dystonia. Canulas were connected to programmed micropumps (iPRECIO® SMP-200) for chronic infusion. Dystonic symptoms were evaluated using a modified version of the BFM scale. Recordings were conducted using high impedance tungsten microelectrodes (Alpha Omega, Israël) and targeted the striatum and pallidal regions during control condition (NaCl- infusion) and Oxotremorin infusion. Sampling frequency was 20KHz. Firing rate, CV ISI and autocorrelation were measured for each well isolated unit. Power spectral density of LFP and Multi-unit-activity were computed with Welch's method (3s window, 50% overlap, spectral resolution of 1/3 Hz). FR, CV ISI and LFP power were compared using non parametric Mann & Whitney test.

 Chronic infusion of non-selective muscarinic agonist (oxotremorininto the putamen of NHPled to:(i) abnormal postures and dystonic movements supported by electromyographic recordings; (ii) drastic changes in the firing rate of striatal, external and internal pallidum neurons with increased burstiness; (iii) changes in oscillatory activity within the striato-pallidal structures with prominent theta activity and decreasebeta band oscillatory power. 


This data directly demonstrates for the first time in non-human primate that cholinergic system dysregulation plays a critical role in the pathophysiology of dystonia.
Edouard Courtin
Dr. Courtin has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file