Pituitary Adenylate Cyclase-Activating Peptide (PACAP) in the Retinohypothalamic Tract: A Potential Daytime Regulator of the Biological Clock

摘要: The retinohypothalamic tract (RHT) relays photic information from the eyes to suprachiasmatic nucleus (SCN). Activation of this pathway by light plays a role in adjusting circadian timing via glutamatergic at night. Here we report new signaling which RHT may regulate daytime as well. We used dual immunocytochemistry for pituitary adenylate cyclase-activating peptide (PACAP) and vivo tracer cholera toxin subunit B observed intense PACAP-immunoreactivity (PACAP-IR) retinal afferents rat SCN well intergeniculate leaflet (IGL) thalamus. This PACAP-IR IGL was nearly lost after bilateral eye enucleation. PACAP originated small ganglion cells distributed throughout retina. phase rhythm measured neuronal activity vitro significantly advanced (3.5 ± 0.4 hr) application 1 × 10−6 m PACAP-38 during subjective day [circadian time (CT)-6] but not night (CT14 CT19). phase-shifting effect is channeled clock PACAP-R1 receptor, because mRNA receptor demonstrated ventral situ hybridization. Furthermore, vasoactive intestinal 1000-fold less potent stimulating advance CT6. mechanism through cAMP-dependent pathway, could be blocked specific cAMP antagonist, Rp-cAMPS. Thus, addition its nocturnal regulation neurotransmission, adjust biological PACAP/cAMP-dependent daytime.