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

• Published in: Nature communications 2020-03, Vol.11 (1), p.1570-1570, Article 1570
• Main Authors: Crompe, Brice de la, Aristieta, Asier, Leblois, Arthur, Elsherbiny, Salma, Boraud, Thomas, Mallet, Nicolas P.
• Format: Article
• Language: English
• Subjects: 631/378; 631/378/3920; 64/86; 96/109; 96/63; Action Potentials - physiology; Animals; Basal ganglia; Basal Ganglia - physiopathology; Beta Rhythm; Brain diseases; Central nervous system diseases; Cerebral cortex; Circuits; Disease Models, Animal; Dopamine; Firing rate; Frequency ranges; Ganglia; Globus pallidus; Globus Pallidus - physiopathology; Humanities and Social Sciences; Life Sciences; Motor Cortex - physiopathology; Movement disorders; multidisciplinary; Nerve Net - physiopathology; Neurodegenerative diseases; Neurons - metabolism; Neurons and Cognition; Optogenetics; Oxidopamine; Parkinson's disease; Parkinsonian Disorders - physiopathology; Rats; Science; Science (multidisciplinary); Spikes; Subthalamic nucleus; Subthalamic Nucleus - physiopathology; Synchronism; Synchronization
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15352-3

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. Oscillatory changes between basal ganglia nuclei occur in Parkinson’s disease. Here the authors determine that the globus pallidus is the source of beta oscillation generation in a rodent model of the disease.