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The Role of the Centromedian-Parafascicular Complex in the Origin and Pathophysiology of Parkinson's Disease

This study will explore the role of the centromedian (CM)-carafascicular (Pf) thalamic complex in the pathophysiology of Parkinson's disease. We expect to confirm in an animal a common origin in the CM-Pf striatal projections linked to the "direct" circuit and connections to the subthalamic nucleus (STN) in the "indirect" circuit, thus confirming our current finding in an animal. The physiological characteristics and relative functional significance of both circuits will be assessed in the animal by microstimulation and by recording neuronal activity in the different circuits. Changes in the CM-Pf relative to modifications of neuronal activity in the STN and pedunculopontine nucleus associated with dopamine depletion (by 6-hydroxydopamine) in the animal will be studied by recording neuronal activity in different periods post-lesion or deafferentation of the CM-Pf will be assessed in normal and MPTP-treated animals with and without levodopa-induced dyskinesias. We expect to demonstrate that the CM-Pf is an important component of the network involved in the pathophysiological origin of PD. The excitatory nature of CM-Pf efferent connections and its presumed hyperactivity in the parkinsonian state lead us to suggest a putative role in the progression of PD, which would be amenable to new therapeutic approaches.


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