Dynamic respiration-neural coupling in substantia nigra across sleep and anesthesia

Respiration is increasingly recognized as a coordinator of neural activity across widespread brain regions and behavioral states. Even during sleep, respiration rhythms modulate sleep-related oscillations. While the basal ganglia are known to play roles in both sleep and respiratory regulation, their interaction with respiration rhythms remains poorly understood. Here, we examined respiration-neural couplings in the substantia nigra pars reticulata (SNr), a major output nucleus of the basal ganglia, and the primary motor cortex (M1) across multiple states in male and female mice, including non-rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, quiet wakefulness, and anesthesia. Simultaneous recordings of local field potentials (LFPs) from M1 and SNr along with diaphragm muscle activities revealed state-dependent, region specific patterns of respiration-neural coupling. Coupling strength in both SNr and M1 was attenuated during NREM sleep compared to REM sleep and quiet wakefulness. However, under ketamine/xylazine anesthesia, coupling was markedly enhanced in the SNr, but not in M1, indicating region-specific sensitivity to arousal and anesthesia state. Notably, respiration-neural coupling was systematically related to delta sub-band power; coupling strength was reduced with increased slow delta (0.5-2 Hz) and decreased fast delta (2.5-4 Hz) powers. In addition, slow delta was associated with SNr-M1 synchronization, suggesting that inter-regional communication during deep sleep may suppress respiration locking. Together, these findings highlight dynamic, state- dependent modulation of respiration-neural couplings in cortico-basal ganglia circuits, underscoring its potential role in coordinating body-brain interactions during sleep and anesthesia.