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Thèse de Marine Chazalon.

"Caractérisation de la transmission GABAergique dans le globus pallidus externe chez des modèles rongeurs des maladies de Parkinson et de Huntington »

Le 18 décembre 2015

Salle de conf de l'Institut Magendie Thèse de Marine Chazalon. 
Directeur Jérôme Baufreton   de l'IMN. Soutenance à 14h .

 The basal ganglia (BG) are a group of sub-cortical nuclei involved in motor, memory and cognitive functions.
In the BG, the GABAergic external globus pallidus (GPe) holds a position of relay nucleus between the striatum (STR) and the subthalamic nucleus within the indirect pathway of the BG.

Modifications of rate and pattern of activity of this nucleus are known to be the electrophysiological signatures of Parkinson’s (PD) and Huntington’s diseases (HD). In PD, hyperactivity of the striato-pallidal (STR-GPe) pathway is thought to be responsible for the increase of the extracellular GABAergic concentrations in the GPe and participate to the hypoactivity of pallidal neurons observed in experimental Parkinsonism. In contrast, during HD, it is recognized that the hyperactivity of GPe neurons is due to the degeneration of striato-pallidal neurons and thus to the reduction of the main source of pallidal GABAergic inhibition.

However, the molecular mechanisms involved in these modifications of pallidal activity are not well characterized. Therefore, using PD and HD animal models, the 6-OHDA rodents and the R6-1 transgenic mice respectively, we have performed molecular biology, immunohistochemistry and electrophysiological in vitro experiments in order to better understand the origin of GABAergic transmission alterations leading to changes in electrophysiological activity of GPe neurons into these two pathologies.

My main results show the apparition of a tonic GABAergic inhibition due to a deficit of GABA uptake in PD and a early stage reduction of GABAergic synaptic transmission in HD. Altogether, these results suggest that alterations of GABAergic transmission contribute to the pathophysiology of PD and HD.