Effects of T-type and L-type calcium currents on synchronized activity patterns in a model subthalamo-pallidal...

Synchronized rhythmic oscillatory activity in the beta frequency band in the basal ganglia (BG) is a hallmark of Parkinson's disease (PD). Recent experiments and theoretical studies have demonstrated the crucial roles of T-type and L-type calcium currents in shaping the activity patterns of subthalamic nucleus (STN) neurons. However, the role of these currents in the generation of synchronized activity patterns in BG networks involving STN is still unknown. In this study, using an STN model incorporating T-type and L-type calcium currents, we examined how these currents shape the patterns of neural activity in a subthalamo-pallidal network, including network dynamics in response to periodic external inputs. The dynamics were studied in relation to the network connectivity parameters-modulated by dopamine (depleted in PD's BG)-and compared with the properties of the temporal patterning of synchronous neural activity previously observed in the experimental studies with Parkinsonian patients. Stronger T-type current enhanced post-inhibitory rebound bursting and expanded synchronized rhythmic activity, reducing the range of intermittent synchrony and increasing resistance to external entrainment. Stronger L-type current prolonged STN bursts, promoted intermittent synchrony over a wide range of input amplitudes, and sustained beta oscillations, suggesting a potential role in the pathophysiology of PD. These results highlight the interplay between intrinsic cellular properties, synaptic parameters, and external inputs in shaping pathological synchronized rhythms in BG networks. Understanding these network mechanisms may advance the understanding of Parkinsonian rhythmogenesis and further assist in finding ways to modulate and suppress pathological rhythms.