Description:

Dr. Aryn Gittis, Ph.D., Department of Biological Sciences and the Neuroscience Institute at Carnegie Mellon University

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.  In dopamine depleted mice, burst-DBS stimulation optimized for cell-type specificity induced motor recovery with sustained therapeutic benefits that persisted for hours after the offset of stimulation.  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 in humans.