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Brice DE LA CROMPE DE LA BOISSIERE

Etude dynamique de la génération des oscillations beta dans la maladie de Parkinson: Approche électrophysiologique et optogénétique

décembre 2016 Directeur(s) de thèse : Thomas Boraud Résumé de thèse

The basal-ganglia (BG) form a complex loop with the cortex and the thalamus that is involved in action selection and movement control. Synchronized oscillatory activities in basal-ganglia neuronal circuits have been proposed to play a key role in coordinating information flow within this neuronal network. If synchronized oscillatory activities are important for normal motor function, their dysregulation in space and time could be pathological. Indeed, in Parkinson’s disease (PD), many studies have reported an abnormal increase in the expression level of neuronal oscillations contain in the beta (β) frequency range (15-30 Hz). These abnormal β oscillations have been correlated with two mains symptoms of PD: akinesia/bradykinesia. However, which BG neuronal circuits generate those abnormal β oscillations, and whether they play a causal role in PD motor dysfunction is not known. The subthalamic nucleus (STN) is a key nucleus in BG that receives converging inputs from the motor cortex, the parafascicular thalamic nucleus and the globus pallidus. Here, we used a rat model of PD combined with in vivo electrophysiological recordings and optogenetic silencing to investigate how selective manipulation of STN inputs causally influence BG network dynamic. Our data highlight the causal role of the globus pallidus in the generation and propagation mechanisms of abnormal β-oscillations.

Key-words: Parkinson’s disease, β oscillation (Beta), basal ganglia, globus pallidus, motor cortex, parafascicular thalamic nucleus, optogenetics, in vivo electrophysiology, juxtacellular labeling.

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