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Dynamics and control of Striatal Neuronal Assemblies in Parkinson's disease: DySNAPark

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease. PD prevalence increases with age and about 1% of the population over 60 is affected by it. With increasing life span, the number of PD- patients is likely to increase and entails significant social and financial costs. While deep-brain stimulation (DBS) and levo-dopa-based treatments alleviate motor symptoms of PD, the cognitive and the emotional disorders continue to exacerbate. This suggests that there is more to PD than just tremor and beta-band oscillations. Indeed, both experimental and theoretical studies suggest that several non-motor symptoms of PD can be attributed to the altered striatal activity dynamics and cortico-striatal interactions, impairing conditions for normal network function.

In this project, funded by the German-Israel Foundation, scientists at the Bernstein Center Freiburg (Arvind Kumar, Ad Aertsen, Sebastian Spreizer) and at the Hebrew University Jerusalem (Hagai Bergman) are combining their theoretical and experimental approaches to extend our understanding of PD beyond motor deficits and oscillatory activity.

The goal of the project is to identify conditions that support the existence of a sufficiently rich repertoire of striatal activity states and transition dynamics to warrant adequate network function. Specifically, by combining multi-site recording studies in primate PD models with computational network models of the key basal ganglia structure we are testing the hypothesis that a rich repertoire of behavior entails the existence of multiple neural assemblies in the striatum and that dopamine depletion-induced changes in activity and correlations destroy these neural assemblies.

When successful, this research will not only improve our understanding of the cortico-striatal activity dynamics, but will also help in identifying novel stimulation paradigms that can restore the altered activity dynamics in the striatum and, thereby, alleviate both motor and non-motor symptoms of PD.

This study is being funded by the German-Israeli Foundation for Scientific Research and Development (GIF) for three years (Jan 2014 – Dec 2016).




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