Dopamine depletion induces low frequency beta oscillations through a minimal loop in basal ganglia: A computational...

Pathological β-band oscillations in the cortex and basal ganglia (BG) are a core electrophysiological hallmark of Parkinson's disease (PD), yet the precise circuits and temporal dynamics governing their emergence remain incompletely understood. To address this, we developed a computational model of the chronically dopamine-depleted BG and identified a minimal inhibitory microcircuit as a primary generator of network wide β oscillations, which is composed of D2-medium spiny neurons (D2-MSN), fast spiking interneurons (FSI), and prototypic external globus pallidus neurons (GPe-TI). By simulating progressive dopamine loss, we show that distinct synaptic pathways within this loop are engaged in a stage-dependent manner: FSI → D2-MSN projection dominates during early to mid depletion stages, whereas GPe-TI → FSI inhibition prevails in later phases. This temporal shift is accompanied by a progressive slowing of the peak oscillation frequency from 11-13 Hz oscillation to 9-11 Hz oscillation. Overall, our results provide a dynamic, circuit level account for how pathological β rhythms evolve over the course of dopamine depletion, offering a mechanistic framework for understanding stage specific pathophysiology in PD and a novel paradigm for designing adaptive neuromodulation strategies.