Basal ganglia activity: The good, the bad, and the depressed

I will present some results relating to recorded activity and simulations of activity in several different regions of the basal ganglia under several different conditions. First, I will discuss simultaneous recordings of single unit activity from the internal segment of the globus pallidus (GPi) and VLa-thalamus in healthy non-human primates during performance of a highly standardized movement task. In contrast to theories of gating and entrainment of VLa by GPi, we observed that changes in firing rates during task-related movement were dominated by increases in both areas with responses in VLa generally leading those in GPi and with weak impact of GPi bursts and pauses on VLa activity. Second, I will discuss results from computational modeling of the pallidostriatal circuit, guided by experimental results characterizing some of its synaptic connections. Our findings predict that the pallidostriatal pathway influences striatal output preferentially during periods of synchronized activity within the external segment of the globus pallidus (GPe) and that, under dopamine-depleted conditions, this effect becomes a key component of a positive feedback loop between the GPe and striatum that promotes synchronization and rhythmicity. Finally, I will discuss additional computational modeling relating to the possible mechanisms of efficacy of deep brain stimulation (DBS) applied in the subthalamic nucleus (STN) in parkinsonism. This work illustrates how synaptic and axonal short-term depression can decouple STN signaling from pathological upstream activity, thereby providing a mechanism to realize the previously proposed idea of a DBS-induced information lesion.