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Selective deficits in the circadian light response in mice lacking PACAP
C S Colwell1, S Michel, J Itri
1Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90024-1759, USA. ccolwell@mednet.ucla.edu
Summary
Pituitary adenylyl cyclase-activating peptide (PACAP) is crucial for the circadian system's light response. PACAP-deficient mice show impaired responses to light, affecting circadian phase shifts.
Area of Science:
- Neuroscience
- Chronobiology
- Molecular Biology
Background:
- Light information reaches the suprachiasmatic nucleus via retinal ganglion cells containing glutamate and pituitary adenylyl cyclase-activating peptide (PACAP).
- The role of glutamate is well-understood, but PACAP's function in this pathway is emerging.
Purpose of the Study:
- To investigate the in vivo functions of PACAP in the mammalian circadian system.
- To determine the specific effects of PACAP deficiency on light-induced responses.
Main Methods:
- Development of a PACAP-deficient mouse model using targeted homologous recombination.
- Radioimmunoassay (RIA) to confirm the absence of PACAP protein.
- Assessment of circadian rhythmicity and light/dark responses.
Main Results:
- PACAP-deficient mice showed significant impairment in light-induced circadian phase delays and advances.
- Both bright and dim light exposures equally affected phase shifts in PACAP-deficient mice.
- Loss of PACAP had minimal impact on the generation of circadian oscillations and masking (light-induced inhibition of activity).
Conclusions:
- PACAP plays a selective role in mediating the circadian system's response to light.
- The findings highlight PACAP's importance in photic entrainment of circadian rhythms.