Synaptic alterations in the indirect-pathway of the basal ganglia in experimental Parkinsonism

My laboratory is interested in understanding the synaptic and cellular mechanisms governing information transfer in the basal ganglia. This network is composed of a group of interconnected subcortical brain nuclei that are critical for voluntary movement, learning and motivation, and the primary site of dysfunction in motor-related disorders such as Parkinson´s disease (PD) and Huntington´s disease (HD). Our objectives are to define the principles underlying the normal and pathophysiological operation of the basal ganglia. Our hope is that this information will provide a better understanding of the molecular mechanisms contributing to PD and HD and will be useful in developing new therapeutic strategies that more effectively treat the symptoms of these disorders.

We utilize multiple experimental approaches including electrophysiology (patch-clamp and extracellular multi-units recordings), calcium imaging, molecular profiling, optogenetics ex vivo and in vivo, neuronal tracing and immunohistochemistry. We combined all these approaches to decipher: 1) the role of specific neuronal subpopulations in motor control, 2) synaptic transmission and plasticity of GABAergic and glutamatergic synapses of the basal ganglia network, 3) the cellular and molecular mechanisms of deep brain stimulation of the subthalamic nucleus (STN-DBS). Our research is supported by the Agence National de la Recherche, the French Parkinson’s disease association and la Fondation de France.