Identification and Functional Dissection of Deep brain Stimulation Circuitry

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

DESCRIPTION (provided by applicant): Targeted electrical stimulation of diverse brain regions, termed deep brain stimulation (DBS), has rapidly come into widespread clinical use for treating neurodegenerative and psychiatric disorders. The most common application of DBS is for the treatment of Parkinson's disease (PD), where DBS has shown enormous efficacy in alleviating devastating motor dysfunction. Despite the great potential of this clinical tool, very little is known about how DBS actually works, which greatly limits refinement of this approach and its extension towards the treatment of additional brain diseases. The proposed project will use a rat model of PD to examine how DBS therapy alters global brain activity. The rat model to be used in this project closely mimics the neurodegeneration seen in human PD patients, and motor symptoms in these rats can also be treated by many of the same therapies used in humans, including DBS. We will use neuroimaging procedures to identify brain areas modulated by DBS in the PD rat, and also evaluate if these modulated brain circuits contribute towards DBS efficacy. For the latter set of experiments, the cutting-edge toolset of optogenetics will be used, whereby the activity of neural circuits can be selectively suppressed. Brain regions modulated by DBS will be systematically shut down during DBS therapy, and the ability of the compromised DBS to restore motor function will be evaluated. This project has the enormous potential to provide critical insights regarding the neuroanatomical mechanisms by which DBS serves as an effective therapy for PD.