Synaptic changes in pallidostriatal circuits observed in parkinsonian model triggers abnormal beta synchrony with accurate spatio-temporal properties across the basal ganglia

• Published in: bioRxiv
• Main Authors: Shiva Azizpour Lindi, Mallet, Nicolas P, Leblois, Arthur
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 10.03.2023
• Subjects: Basal ganglia; Central nervous system diseases; Cortex (motor); Cortex (temporal); Electrical stimuli; Firing pattern; Firing rate; Globus pallidus; Movement disorders; Neostriatum; Neural networks; Neurodegenerative diseases; Oscillations; Parkinson's disease; Solitary tract nucleus; Subthalamic nucleus
• DOI: 10.1101/2023.03.07.531640

Excessive oscillatory activity across basal ganglia (BG) nuclei in the β frequencies (12–30Hz) is a hallmark of Parkinson's disease (PD). While the link between oscillations and symptoms remains debated, exaggerated β oscillations constitute an important biomarker for therapeutic effectiveness in PD. The neuronal mechanisms of β-oscillation generation however remain unknown. Many existing models rely on a central role of the subthalamic nucleus (STN) or cortical inputs to BG. Contrarily, neural recordings and optogenetic manipulations in normal and parkinsonian rats recently highlighted the central role of the external pallidum (GPe) in abnormal β oscillations, while showing that the integrity of STN or motor cortex is not required. Here, we evaluate the mechanisms for the generation of abnormal β oscillations in a BG network model where neuronal and synaptic time constants, connectivity, and firing rate distributions are strongly constrained by experimental data. Guided by a mean-field approach, we show in a spiking neural network that several BG sub-circuits can drive oscillations. Strong recurrent STN-GPe connections or collateral intra-GPe connections drive gamma oscillations (>40Hz), whereas strong pallidostriatal loops drive low-β (10–15Hz) oscillations. We show that pathophysiological strengthening of striatal and pallidal synapses following dopamine depletion leads to the emergence of synchronized oscillatory activity in the mid-β range with spike-phase relationships between BG neuronal populations in-line with experiments. Furthermore, inhibition of GPe, contrary to STN, abolishes oscillations. Our modeling study uncovers the neural mechanisms underlying PD β oscillations and may thereby guide the future development of therapeutic strategies.Competing Interest StatementThe authors have declared no competing interest.