The globus pallidus orchestrates abnormal network dynamics in a model of Parkinsonism

Brice De La Crompe,Thomas Boraud,Nicolas P Mallet,Arthur Leblois,Asier Aristieta,Salma Elsherbiny

doi:10.1038/s41467-020-15352-3

Abstract

The dynamical properties of cortico-basal ganglia (CBG) circuits are dramatically altered following the loss of dopamine in Parkinson’s disease (PD). The neural circuit dysfunctions associated with PD include spike-rate alteration concomitant with excessive oscillatory spike-synchronization in the beta frequency range (12–30 Hz). Which neuronal circuits orchestrate and propagate these abnormal neural dynamics in CBG remains unknown. In this work, we combine in vivo electrophysiological recordings with advanced optogenetic manipulations in normal and 6-OHDA rats to shed light on the mechanistic principle underlying circuit dysfunction in PD. Our results show that abnormal neural dynamics present in a rat model of PD do not rely on cortical or subthalamic nucleus activity but critically dependent on globus pallidus (GP) integrity. Our findings highlight the pivotal role played by the GP which operates as a hub nucleus capable of orchestrating firing rate and synchronization changes across CBG circuits both in normal and pathological conditions.

Highlights

The dynamical properties of cortico-basal ganglia (CBG) circuits are dramatically altered following the loss of dopamine in Parkinson’s disease (PD)
Dopaminergic loss in the striatum triggers an imbalance in the firing activity of striatal neurons involved in BG direct and indirect pathways, resulting in a cascade of firing rate changes along these circuits which leads to an overinhibition of the motor system[4,5]
We combined in vivo electrophysiological recordings in normal and parkinsonian rats with optogenetic manipulations to dissect the specific functional contribution of key cortico-basal ganglia (CBG) components and understand how the generation/propagation of abnormal firing rate and synchronized oscillatory activity in PD is orchestrated

Summary

Introduction

The dynamical properties of cortico-basal ganglia (CBG) circuits are dramatically altered following the loss of dopamine in Parkinson’s disease (PD). We combined in vivo electrophysiological recordings in normal and parkinsonian rats with optogenetic manipulations (i.e., opto-excitation and optoinhibition) to dissect the specific functional contribution of key cortico-basal ganglia (CBG) components (i.e., the motor cortex, the STN, and the GP) and understand how the generation/propagation of abnormal firing rate and synchronized oscillatory activity in PD is orchestrated.

Results

Conclusion