Sleep period noise induces wakefulness via the paraventricular thalamic lateral septum circuit in mice

Environmental noise exposure disrupts sleep architecture by inducing sleep-wake state transitions (SWSTs) or reducing continuity. This study examined patterns of noise-induced SWST and underlying neural circuit mechanisms. White noise (45 dB SNR) induced SWST and increased paraventricular thalamic (PVT) neuronal activity. In vivo fiber photometry revealed increased calcium signaling in PVT glutamatergic neurons prior to noise-induced arousal. Optogenetic/chemogenetic PVT inactivation prolonged latency to arousal and reduced arousal probability. Viral tracing and immunofluorescence revealed dense glutamatergic projections from the PVT that are in close spatial apposition to GABAergic neurons within the intermediate part of the lateral septum (LSI). Projection-specific optogenetic inhibition of PVT terminals in the LSI successfully suppressed noise-induced SWST. These results identify the LSI as a critical functional downstream target of PVT glutamatergic neurons in mediating acoustic arousal, providing a potential neural target for intervening in noise-induced sleep fragmentation.