Nonlinear dynamics of arkypallidal neurons in the basal ganglia network: Mechanisms and therapeutic implications for Parkinson’s disease

Parkinson’s disease (PD) causes motor deficits via an imbalance between the basal ganglia (BG) direct and indirect pathways. Anatomically, a subset of globus pallidus externus (GPe) neurons-arkypallidal (GPe-TA)-provides inhibitory feedback to the striatum and thereby bridges the pathways, while the hyperdirect subthalamic nucleus (STN) excites the GPe, positioning it as a relay hub. We develop an extended BG model in a modified Hodgkin–Huxley framework that separates GPe-TA from prototypic (GPe-TI) neurons and use it to run circuit-specific optogenetic simulations as a targeted alternative to deep brain stimulation (DBS). The model reproduces the GPe’s functional asymmetry and identifies GPe-TA as a mediator of pathway integration: exciting GPe-TA shifts network activity toward direct-pathway dominance. We test four protocols-exciting D1 medium spiny neurons (D1 MSNs), exciting the globus pallidus internus (GPi), exciting GPe-TA, and inhibiting GPe-TI-across frequency and pulse-width grids, using an error index (EI) to score outcomes. D1 MSN excitation yields the highest success rate, while GPe-TA excitation achieves comparable efficacy at the lowest duty cycle (8%; 40 Hz, 2 ms). Framed by a nonlinear-dynamics perspective in which coupling structure and synaptic kinetics shape oscillatory and synchronization regimes, these results support circuit-specific, low-duty-cycle optogenetic options for PD and guide stimulation-parameter selection.