Protein Kinase C Differentially Regulates Entrainment of the Mammalian Circadian Clock

Abstract

The environmental day-night cycle provides the principal synchronizing signal for behavioral activity in most mammals. Light information is relayed to the master circadian pacemaker, the suprachiasmatic nucleus (SCN), via synaptic transmission from the retina directly to the SCN, where a predominately glutamate-driven cellular signaling pathway is able to reset biochemical, physiological, and behavioral activities. In the present study, we aimed to decipher the key roles played by protein kinase C (PKC) in regulating light-induced behavioral resetting under both a temporal and intensity-dependent manner; in addition, we also investigate PKC contributions to advancing and delaying re-entrainment paradigms. Our findings show that during the early night PKC acts in a temporal manner, where PKC inhibition selectively attenuates light-induced behavioral resetting in response to subsaturating and saturating light intensities. Declines in light response were also evident upon PKC inhibition during the late night, but restricted to bright light stimuli. The positive regulatory actions of PKC were further demonstrated in response to an 8-h delayed re-entrainment paradigm where inhibition of PKC resulted in slower re-entrainment. Further, analysis of both classic and novel PKC isozymes present within the SCN showed significant circadian variation in the mRNA expression of PKCα, indicating possible isozyme-specific mediators in photic signaling. Our data provide evidence of a PKC contribution to both acute light-induced clock resetting, which is intensity and time of day dependent, and a functional role in circadian photoentrainment. (Author correspondence: [email protected])

Keywords:

• Clock
• Entrainment
• Light
• Phase shift
• PKC
• Protein kinase C
• Suprachiasmatic nucleus