title: The photopigment melanopsin is exclusively present in pituitary adenylate cyclase-activating polypeptide-containing retinal ganglion cells of the retinohypothalamic tract.
abstract: Mammalian circadian rhythms generated in the hypothalamic suprachiasmatic nuclei are entrained to the environmental light/dark cycle via a monosynaptic pathway, the retinohypothalamic tract (RHT). We have shown previously that retinal ganglion cells containing pituitary adenylate cyclase-activating polypeptide (PACAP) constitute the RHT. Light activates the RHT via unknown photoreceptors different from the classical photoreceptors located in the outer retina. Two types of photopigments, melanopsin and the cryptochromes (CRY1 and CRY2), both of which are located in the inner retina, have been suggested as "circadian photopigments." In the present study, we cloned rat melanopsin photopigment cDNA and produced a specific melanopsin antibody. Using in situ hybridization histochemistry combined with immunohistochemistry, we demonstrate that the distribution of melanopsin was identical to that of the PACAP-containing retinal ganglion cells. Colocalization studies using the specific melanopsin antibody and/or cRNA probes in combination with PACAP immunostaining revealed that melanopsin was found exclusively in the PACAP-containing retinal ganglion cells located at the surface of somata and dendrites. These data, in conjunction with published action spectra analyses and work in retinally degenerated (rd/rd/cl) mutant mice, suggest that melanopsin is a circadian photopigment located in retinal ganglion cells projecting to the biological clock.
authors.affiliation: Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen, Denmark. J.Hannibal@inet.uni2.dk
authors.forename: Jens
authors.initials: J
authors.lastname: Hannibal
authors.forename: Peter
authors.initials: P
authors.lastname: Hindersson
authors.forename: Sanne M
authors.initials: SM
authors.lastname: Knudsen
authors.forename: Birgitte
authors.initials: B
authors.lastname: Georg
authors.forename: Jan
authors.initials: J
authors.lastname: Fahrenkrug
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D002452:Cell Count; D003001:Cloning, Molecular; D007031:Hypothalamus / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D009928:Organ Specificity; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology* / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D017299:Rod Opsins / Q000096:biosynthesis* / Q000235:genetics; D000099210:Melanopsin
chemical_list: D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D017299:Rod Opsins; D000099210:Melanopsin; C495403:Adcyap1 protein, rat