Gamma oscillations in basal ganglia stem from the interplay between local inhibition and beta synchronization
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Basal ganglia activity fluctuations have primarily been studied in the context of beta (12-30 Hz) oscillations, a well-established neural marker for Parkinson’s Disease (PD). Recent studies have also identified gamma (30-100 Hz) oscillations within the basal ganglia, suggesting it could serve as an alternative marker, but the underlying circuit mechanisms remain poorly understood. Here, through a spiking network model of the basal ganglia, we identified two distinct gamma oscillations: a high-frequency gamma rhythm within the globus pallidus (GPe-TI) and a slower gamma rhythm within D2 medium spiny neurons (MSNs), both stemming from self-inhibition. When we simulated dopamine depletion to mimic the effects of PD, the intensity of gamma oscillations in the GPe-TI was not affected, but their peak frequency increased due to phase-amplitude coupling with pathological beta oscillations. This suggests that the GPe-TI loop, while robust to dopamine depletion, becomes more synchronized with beta activity in the context of PD, leading to faster gamma rhythms. In contrast, gamma oscillations in D2 MSNs were not present in simulated healthy condition and only emerged under dopamine-depleted pathological conditions. Moreover, both their intensity and peak frequency were strongly modulated by pathological beta activity.
Together, these findings highlight the complementary roles of self-inhibition and beta oscillations in shaping gamma activity within basal ganglia circuits. The GPe-TI loop primarily sustains high-frequency gamma rhythms, while low frequency gamma rhythms in D2 MSNs are strongly dependent on dopamine-depletion-related beta modulation. These results underscore the importance of network-wide interactions in PD, where pathological beta oscillations influence gamma activity. This study offers insights into the mechanisms of gamma oscillations in PD and highlights the potential of gamma activity, in both the prototypical and striatal loops, as a marker for disease progression and monitoring pathological dysfunction in PD.
Author Summary
Understanding the neural underpinnings of Parkinson’s Disease (PD) is crucial for advancing treatments such as deep brain stimulation. While much research has focused on beta oscillations (12-30 Hz) in the basal ganglia as markers of Parkinsonian states, our study explores the role of gamma oscillations (30-100 Hz), which have been observed experimentally but are less understood. Using a computational model, we identified two distinct types of gamma rhythms: a high-frequency oscillation in the globus pallidus and a slower oscillation in D2 medium spiny neurons.
Our findings reveal that in simulated healthy conditions, gamma oscillations originate within the globus pallidus. However, under conditions mimicking PD, gamma activity in D2 MSNs is also present. Both rhythms stem from local inhibition and are shaped by pathological beta oscillations in both frequency and spectral power.
These results show how gamma oscillations originate in the basal ganglia and how they strongly interact with pathological beta synchronization related to PD. Our study highlights the potential of gamma activity as a valuable marker for guiding deep brain stimulation and understanding the underlying dysfunctions in PD.
