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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)
010

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.
Authors/Disclosures
Edouard Courtin
PRESENTER
Dr. Courtin has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file