Calcium-Based Synaptic and Structural Plasticity Link Pathological Activity to Synaptic Reorganization in Parkinson's Disease

Abstract

Altered motor symptoms of Parkinsons disease (PD) are associated with dopaminergic neuronal loss. Widespread synaptic reorganization and neural activity changes, including exaggerated beta oscillations and bursting, follow dopamine depletion (DD) of the basal ganglia (BG). Our computational model examines DD-induced neural activity changes and synaptic reorganization. It encompasses the BG sub-circuit comprising the subthalamic nucleus and globus pallidus externus. Calcium-dependent synaptic and structural plasticity mechanisms were incorporated, allowing neural activity to alter network topology. We show how elevated iMSN firing rates can induce synaptic connectivity changes consistent with PD animal models. We suggest synaptic reorganization following DD results from a series of homeostatic calcium-based synaptic changes triggered by elevated iMSN activity. Structural plasticity counteracts DD-induced neural activity changes and opposes exaggerated beta oscillations, whereas synaptic plasticity alone amplifies beta oscillations. Our results suggest that synaptic and structural plasticity have qualitatively different contributions to DD-induced synaptic reorganization in the BG. TeaserSynaptic and structural plasticity differentially drive synaptic reorganization and abnormal activity in Parkinsons disease.