Transmission of delta band (0.5-4 Hz) oscillations from the globus pallidus to the substantia nigra pars reticulata in dopamine depletion.

Abstract

Parkinson's disease (PD) and animal models of PD feature enhanced oscillations in several frequency bands in the basal ganglia (BG). Past research has emphasized the enhancement of 13-30 Hz beta oscillations. Recently, however, oscillations in the delta band (0.5-4 Hz) have been identified as a robust predictor of dopamine loss and motor dysfunction in several BG regions in mouse models of PD. In particular, delta oscillations in the substantia nigra pars reticulata (SNr) were shown to lead oscillations in motor cortex (M1) and persist under M1 lesion, but it is not clear where these oscillations are initially generated. In this paper, we use a computational model to study how delta oscillations may arise in the SNr due to projections from the globus pallidus externa (GPe). We propose a network architecture that incorporates inhibition in SNr from oscillating GPe neurons and other SNr neurons. In our simulations, this configuration yields firing patterns in model SNr neurons that match those measured in vivo. In particular, we see the spontaneous emergence of near-antiphase active-predicting and inactive-predicting neural populations in the SNr, which persist under the inclusion of STN inputs based on experimental recordings. These results demonstrate how delta oscillations can propagate through BG nuclei despite imperfect oscillatory synchrony in the source site, narrowing down potential targets for the source of delta oscillations in PD models and giving new insight into the dynamics of SNr oscillations.