The paraventricular thalamus is required for homeostatic sleep regulation by adenosine

BACKGROUND AND PURPOSE: Adenosine has been proposed as a prominent mediator of sleep homeostasis. Adenosine accumulation during wakefulness induces transitions to non-rapid eye movement (NREM) sleep. However, the precise neural mechanisms underlying the homeostatic regulation of sleep by adenosine have not been fully elucidated. EXPERIMENTAL APPROACH: All experiments were conducted in male mice. Genetically-encoded adenosine sensors were used to assess the dynamic fluctuations of extracellular adenosine in the paraventricular thalamus (PVT). We performed whole-cell patch-clamp recordings in vitro to investigate the effects of adenosine on PVT neurons, and combined these experiments with fibre photometry and multi-channel electrophysiological recordings in vivo. Electroencephalogram (EEG)/electromyogram (EMG) recordings were used to investigate the role of adenosine in regulating wakefulness and sleep, together with drug administration, sleep deprivation (SD) and RNA interference (RNAi). KEY RESULTS: Rs). CONCLUSION AND IMPLICATIONS: These results revealed that homeostatic sleep regulation by adenosine requires the PVT, adding new insights into the homeostatic regulation of sleep.