Mark Bevan

3 octobre 2018

Attention c’est un mercredi

Northwestern University, Feinberg School of Medicine, Chicago, IL, USA

Plasticity of the subthalamic nucleus in Parkinson’s disease and what it tells us about rate and pattern models of basal ganglia dysfunction

invité par Christelle Baunez


abstract

In toxin models of advanced Parkinson’s disease (PD) basal ganglia neurons exhibit profound alterations in their intrinsic firing and synaptic properties. Dopamine depletion-triggered plasticity appears to be homeostatic in nature, i.e., it opposes the change in the frequency of in vivo activity that results from the loss of dopaminergic neuromodulation. In this talk I will focus on the subthalamic nucleus (STN), a key component of the co-called indirect and hyperdirect basal ganglia pathways that are thought to be important for movement suppression, and the primary site of deep-brain stimulation for the treatment of PD motor symptoms. Following the loss of dopamine, STN neurons are thought to be abnormally hyperactive in vivo. Consistent with the engagement of homeostatic plasticity in PD mice, STN neurons exhibit downregulated autonomous activity and a decrease in the strength of incoming synaptic excitation versus inhibition. However, chemogenetically restoring autonomous STN activity or preventing cellular and synaptic plasticity through knockdown of STN NMDA receptors ameliorates motor dysfunction, arguing that STN plasticity is in fact maladaptive. I will describe the molecular, cellular, and circuit mechanisms responsible for STN plasticity and explain how these findings challenge the classic rate model of basal ganglia function and dysfunction, and inform the design of novel therapeutic approaches for PD.

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