Role of BDNF signaling for striatal plasticity and motor learning (A05)

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This project is designed to investigate how the release of brain-derived neurotrophic factor (BDNF) from corticostriatal afferents and tropomyosin receptor kinase B (TrkB) responsiveness in striatal medium spiny neurons are regulated by dopaminergic activity from the substantia nigra and by deep brain stimulation (DBS) of the subthalamic nucleus (STN). The project builds on our expertise with cell culture techniques for enrichment of medium spiny neurons and new mouse models of dystonia, as well as models in which BDNF signaling in these corticostriatal synapses is disturbed. The goal is to understand how plasticity mechanisms at this synapse contribute to motor defects in Parkinson´s disease and dystonia, and how DBS of the STN modulates this synapse and motor function.