BMI Seminar // Tanya Sippy: Modulation of striatal neuron membrane potential dynamics by movement

As the input nucleus of the basal ganglia, the striatum has been heavily implicated in the generation and selection of motor commands. Despite this, we know very little about how different types of movement activate D1 and D2 striatal projection neurons (SPNs) that make up the direct and indirect pathways of this structure. To investigate this, we conducted in vivo whole-cell membrane potential (Vm) recordings from D1 and D2 SPNs in the striatum of head-fixed mice in three behavioral paradigms – (1) under anesthesia, (2) awake on a stationary platform, and (3) awake on a mobile disk. Under anesthesia, Vm is bimodal, exhibiting slow-wave fluctuations at 1 – 4 Hz. However, bimodality is progressively attenuated in awake motor states, with largely unimodal Vm dynamics present in animals on a mobile disk. We then characterized how different types of movement activate D1- and D2 SPNs. We found that, for animals on the stationary platform, orofacial movements such as whisking and grooming evoke larger and faster depolarizations in D1-SPNs compared to D2-SPNs. In contrast, in animals on the mobile disk, D1 and D2 SPNs showed similar depolarizations at movement onset. Finally, we found that chronic dopamine depletion abolished cell type specific recruitment during facial movements. Our work finds evidence for both biased and parallel activation of direct and indirect pathways depending on movement type, with biased activation requiring intact dopamine signaling.