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

Excessive oscillatory activity across basal ganglia (BG) nuclei in the {beta} frequencies (12-30Hz) is a hallmark of Parkinsons disease (PD). While the link between oscillations and symptoms remains debated, exaggerated {beta} oscillations constitute an important biomarker for therapeutic effectiveness in PD. The neuronal mechanisms of {beta}-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 {beta} oscillations, while showing that the integrity of STN or motor cortex is not required. Here, we evaluate the mechanisms for the generation of abnormal {beta} 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-{beta} (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-{beta} 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 {beta} oscillations and may thereby guide the future development of therapeutic strategies. Significance statementIn Parkinsons disease, neural activity in subcortical nuclei called the basal ganglia displays abnormal oscillatory synchronization that constitutes an important biomarker for therapeutic effectiveness. The neural mechanisms for the generation of these oscillations remain unknown. Here, in a theoretical neuronal network model strongly constrained by anatomical and physiological data, we show that specific circuit modifications in basal ganglia connectivity during Parkinsons disease lead to the emergence of synchronized oscillatory activity in the network with properties that strongly agree with available experimental evidence. This and future theoretical investigations of the neural mechanisms underlying abnormal neuronal activity in Parkinsons disease are necessary to guide the future development of therapeutic strategies to ameliorate symptoms.