Schor, J. S. | bioRxiv Science

bioRxiv2021

Therapeutic Deep Brain Stimulation Disrupts Subthalamic Nucleus Activity Dynamics in Parkinsonian Mice

Subthalamic nucleus deep brain stimulation (STN DBS) relieves many motor symptoms of Parkinsons Disease (PD), but its underlying therapeutic mechanisms remain unclear. Since its advent, three major theories have been proposed: (1) DBS inhibits the STN and basal ganglia output; (2) DBS antidromically activates motor cortex; and (3) DBS disrupts firing dynamics within the STN. Previously, stimulation-related electrical artifacts limited mechanistic investigations using electrophysiology. We used electrical artifact-free calcium imaging to investigate activity in basal ganglia nuclei during STN DBS in parkinsonian mice. To test whether the observed changes in activity were sufficient to relieve motor symptoms, we then combined electrophysiological recording with targeted optical DBS protocols. Our findings suggest that STN DBS exerts its therapeutic effect through the disruption of STN dynamics, rather than inhibition or antidromic activation. These results provide insight into optimizing PD treatments and establish an approach for investigating DBS in other neuropsychiatric conditions.

neuroscience↗

bioRxiv2019

Regular cycling between representations of alternatives in the hippocampus

Cognitive faculties such as imagination, planning, and decision-making require the ability to represent alternative scenarios. In animals, split-second decision-making implies that the brain can represent alternatives at a commensurate speed. Yet despite this insight, it has remained unknown whether there exists neural activity that can consistently represent alternatives in <1 s. Here we report that neural activity in the hippocampus, a brain structure vital to cognition, can regularly cycle between representations of alternative locations (bifurcating paths in a maze) at 8 Hz. This cycling dynamic was paced by the internally generated 8 Hz theta rhythm, often occurred in the absence of overt deliberative behavior, and unexpectedly also governed an additional hippocampal representation defined by alternatives (heading direction). These findings implicate a fast, regular, and generalized neural mechanism underlying the representation of competing possibilities.

neuroscience↗