Beta-band bursting activity in computational model of heterogeneous external globus pallidus circuits

Abstract

Exaggerated beta oscillations (13–35 Hz) in basal ganglia (BG) are the hallmark of dynamical properties in Parkinson’s disease (PD). Physiological experiments have shown that different subtypes of external globus pallidus (GPe) exhibit different changes in pathological conditions, which poses a challenge to the classic basal ganglia network modeling of PD, as the mechanism behind some novel phenomenon is almost impossible to reveal by classical models. We propose an extended striatum–GPe model including two subtypes of GPe, the calcium-binding protein parvalbumin GPe (PV GPe) and Lim homeobox 6 GPe (Lhx6 GPe). Based on this model, we illustrate the effect of inhibitory connections in GPe on neural bursting activities. The increase in self-inhibition of homogeneous GPe neurons can expand the spectral power of the beta-band, while mutual inhibition between heterogeneous GPe can regulate the burst of beta-band. Meanwhile, through the discussion about coupling parameters of GPe, we obtain a set of physiological parameters simulated healthy state. Furthermore, we find that both reducing M-current in striatal medium spine neuron (MSN) and degrading PV GPe to Lhx6 GPe could lead to bursting behaviors in PV GPe, and removing the connection from Lhx6 GPe to PV GPe can reduce the power of the beta-band. The role of heterogeneous GPe in Parkinsonian beta-band bursting is also revealed by simulating the specific optogenetic stimulation on GPe. These results demonstrate the facilitation and control function of heterogeneous GPe to abnormal oscillations and provide a novel insight into designing therapeutic interventions.