Calcium-based synaptic and structural plasticity link pathological activity to synaptic reorganization in Parkinson’s disease

TL;DR

This paper explores how calcium-based changes in brain connections may explain abnormal brain activity and symptoms in Parkinson’s disease.

Contribution

The study introduces a computational model linking calcium-dependent plasticity to synaptic reorganization in Parkinson’s disease.

Findings

Hyperactivity of iMSN neurons triggers synaptic changes seen in Parkinson’s animal models.

Calcium-based plasticity compensates for dopamine loss but may fail with excessive bursting activity.

Abstract

Motor symptoms of Parkinson’s 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 in the BG subcircuit 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 hyperactivity of indirect pathway striatal projection neurons (iMSN) can induce synaptic connectivity changes consistent with PD animal models. Our results suggest that synaptic reorganization following DD results from a series of homeostatic calcium–based synaptic changes triggered by iMSN hyperactivity. While this structural plasticity functions as a compensatory mechanism in the cascade of changes following elevated iMSN input from striatal DD, it may become compromised if iMSN and cortical inputs show substantial bursting activity.

Synaptic and structural plasticity differentially drive synaptic reorganization and abnormal activity in Parkinson’s disease.

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