PACAP/PAC 1 modulates light-induced sleep via the ipRGC-VLPO pathway

Light can induce sleep. Many studies have shown that intrinsically photosensitive retinal ganglion cells (ipRGCs) and the ventrolateral preoptic area (VLPO) pathway mediate light-induced sleep. IpRGCs can release the pituitary adenylate cyclase-activating peptide (PACAP), which is involved in the regulation of circadian rhythm. Previous studies have shown that PACAP is closely associated with sleep, but the effect of PACAP on light-induced sleep has not been reported. To investigate the mechanism of PACAP in ipRGC-VLPO light-induced sleep, in vivo EEG recording, immunohistochemistry and in vitro electrophysiological recording were used in this study. Using immunohistochemistry experiments, we found that PACAP and its receptor PAC1 were widely expressed in VLPO. Microdialysis was used to inject the PAC1 agonist PACAP 1-38 into VLPO, and the results showed that the mice's sleep increased, including increased rapid eye movement (REM) sleep and decreased wake. Using brain slice patch clamp technology, we found that PACAP 1-38 increased the excitability of VLPO interneurons while inhibiting the excitability of VLPO sleep-promoting neurons. After the partial destruction of ipRGCs through the intraocular injection of saporin (SAP), we continued to observe the effect of PACAP on light-induced sleep. The results showed that after the microdialysis injection of PACAP 1-38 into the VLPO of SAP mice, the light-induced sleep of the mice increased; specifically, REM sleep significantly increased. The results suggest that PACAP is involved in ipRGC-VLPO-mediated light-induced sleep.