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Am J Physiol Regul Integr Comp Physiol (October 15, 2008). doi:10.1152/ajpregu.90563.2008
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Submitted on July 3, 2008
Revised on October 8, 2008
Accepted on October 13, 2008

Mice lacking the PACAP type I receptor have impaired photic entrainment and negative masking

Jens Hannibal1*, Phillip Brabet, and Jan Fahrenkrug2

1 Rigshospitalet
2 University of Copenhagen

* To whom correspondence should be addressed. E-mail: j.hannibal{at}inet.uni2.dk.

The retinohypothalamic tract (RHT) is a retinofugal neuronal pathway which, in mammals, mediates non-image forming vision to various areas in the brain involved in circadian timing, masking behaviour, and regulation of the pupillary light reflex. The RHT co-stores the two neurotransmitters glutamate and PACAP, which in a rather complex interplay are mediators of photic adjustment of the circadian system. To further characterize the role of PACAP/PAC1 receptor signalling in light entrainment of the clock and in negative masking behaviour, we extended previous studies in mice lacking the PAC1 receptor (PAC1 KO) by examining their phase response to single light pulses using Aschoff type II regime, their ability to entrain to non-24 h LD cycles and large phase shifts of the LD cycle (jetlag), as well as their negative masking response during different light intensities. A prominent finding in PAC1 KO mice was a significantly decreased phase delay of the endogenous rhythm at early night. In accordance, PAC1 KO mice had a reduced ability to entrain to T-cycles longer than 26 h and needed more time to re-entrain to large phase delays, which was prominent at low light intensities. The data obtained at late night indicated that PACAP/PAC1 receptor signalling is less important during the phase advancing part of the phase-response curve. Finally, the PAC1 KO mice showed impaired negative masking behaviour at low light intensities. Our findings substantiate a role for PACAP/PAC1 receptor signalling in non-image forming vision and indicate that the system is particularly important at lower light intensities.




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