Dynamical Mechanism of Parkinsonian Beta Oscillation in a Heterogenous Subthalamopallidal Network

Abstract

Dysfunction of basal ganglia (BG) is associated with the pathogenesis of Parkinson's disease (PD) including alteration of firing rate and excessive beta-band (13-30Hz) synchronization activity. Neuronal heterogeneity enriches dynamics of the nucleus, and heterogeneous external globus pallidus (GPe) neurons exhibit remarkable differences in discharge altering under pathological state. The precise mechanism underlying these neural signatures remains elusive. To address this, we propose a subthalamopallidal network containing two classes of GPe neurons, calcium-binding protein parvalbumin (PV) and Lim homeobox (Lhx6) GPe. Our results show that Lhx6 GPe tends to rein in synchronous behavior and abnormal activity of PV GPe. Under pathological condition, the alteration of synaptic in heterogenous pallidal network manifests itself as a direct increase of inhibitory input to PV GPe or an indirect elevation of Lhx6 GPe firing rate. These essentially enhance the inhibition of PV GPe, which results in beta-band synchronous bursting. STN is instrumental in stabilizing the spiking sequence of GPe neurons, inhibiting abnormal synchronous oscillations both in control and pathological conditions. After dopamine-depleted, the STN-GPe circuit becomes a key component of positive feedback that promotes synchronization and rhythmicity. Among them, the PV-PV pathway notably impacts the enhancement of beta rhythmic oscillations, and the mutual inhibition between heterogenous GPe and STN-GPe synaptic affects the propagation of abnormal rhythms in pallidal and subthalamopallidal network, respectively. Our study highlights the pivotal role played by PV GPe in producing and amplifying pathological oscillatory behavior and STN in preventing abnormal rhythm, providing a novel insight into the design of therapeutic strategies.