Roles of PACAP-containing retinal ganglion cells in circadian timing.
The brain's biological clock located in the suprachiasmatic nucleus (SCN) generates circadian rhythms in physiology and behavior. The clock-driven rhythms need daily adjustment (entrainment) to be synchronized with the astronomical day of 24 h. The most important stimulus for entrainment of the clock is the light-dark (LD) cycle. In this review functional elements of the light entrainment pathway will be considered with special focus on the neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP), which is found exclusively in the monosynaptic neuronal pathway mediating light information to the SCN, the retinohypothalamic tract (RHT). The retinal ganglion cells of the RHT are intrinsically photosensitive due to the expression of melanopsin and seem to constitute a non-image forming photosensitive system in the mammalian eye regulating circadian timing, masking behavior, light-regulated melatonin secretion, and the pupillary light reflex. Evidence from in vitro and in vivo studies and studies of mice lacking PACAP and the specific PACAP receptor (PAC1) indicate that PACAP and glutamate are neurotransmitters in the RHT which in a clock and concentration-dependent manner interact during light entrainment of the clock.
Hannibal
Jens
J
Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Denmark.
D000818:Animals; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D003624:Darkness; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008027:Light; D009434:Neural Pathways / Q000033:anatomy & histology / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D017299:Rod Opsins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism; D000099210:Melanopsin
D018698:Glutamic Acid; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D017299:Rod Opsins; D000099210:Melanopsin