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Mechanisms and Control of Movement Disorders: Ataxia and Parkinson's Disease
Mechanisms and Control of Movement Disorders: Ataxia and Parkinson’s Disease
These researchers are using MSI for two projects. The first involves a novel form of neural activation of the cerebellar cortex that was discovered in the Ebner laboratory using optical imaging methods in vivo. This activation process, called “spreading acidification and depression” (SAD), is hypothesized to underlie the channelopathy of episodic ataxia type 1. The cellular mechanisms of SAD remain unclear. In order to understand these mechanisms, this group has developed a computational model of SAD based on direct activation of the parallel fibers through addition of extra synaptic glutamate. The model uses the geometry of the cerebellar cortex determined through measurements of extrasynaptic diffusion of glutamate in the cerebellar cortex released from local synapses. The model has several free parameters, such as tissue volume, the glutamate activation threshold, and the synaptic release delay. The researchers are performing a systematic sweep of the free parameter space to characterize the model and compare it with the experimental results.
The second project investigates the cerebellum, which plays a major role in controlling goal-directed motor behavior. Crucial in understanding the cerebellar function are deep cerebellar nuclei (DCN). DCN provide a major gateway of the cerebellar output. DCN is also part of the olivo-cerebellar loop that modulates the cerebellar cortex activity through the climbing fibers input to the Purkinje cells. Most of the previous efforts aimed at direct recordings from nuclear neurons used stereotypical and highly predictable paradigms that provided limited insight into cerebellar function. This study will use a more complex and less predictable paradigm that will allow a much more detailed understanding of the DCN contribution to the cerebellar function.
A bibliography of this group’s publications acknowledging MSI is attached.