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Abstract: The identification of distinct cell-types throughout the basal ganglia has been essential in advancing understanding of network function and improving neurological therapies. In the globus pallidus externa (GPe), interventions targeting neuronal subpopulations have profound therapeutic potential, but are challenging to implement in clinical settings. We investigated whether electrical stimulation can be tuned to engage cell-type specific responses in the GPe. Although conventional stimulation was non-specific, brief, high frequency bursts of stimulation elicited bimodal responses of Parvalbumin (PV-GPe) and Lim homeobox 6 (Lhx6-GPe) subpopulations. Using a machine-learning approach, we optimized the cell-type specificity of this approach and developed an in vivo DBS protocol capable of extending the therapeutic benefits of stimulation ~5-fold beyond what is possible using conventional DBS. These results establish the feasibility of shaping electrical stimulation patterns to drive population-specific neuromodulation in the central nervous system, and suggests the potential for developing a more robust toolbox for deep brain stimulation therapies.
Publication: Spix, T. A., Nanivadekar, S., Toong, N., Kaplow, I. M., Isett, B. R., Goksen, Y., Pfenning, A. R., & Gittis, A. H. (2021). Population-specific neuromodulation prolongs therapeutic benefits of deep brain stimulation. In Science (Vol. 374, Issue 6564, pp. 201–206). American Association for the Advancement of Science (AAAS).
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"Circuit-Inspired Strategies to Improve Treatments for Parkinson's Disease"
Event Date:
June 8th 12:00 PM - 1:00 PM
