Altered light induced EGR1 expression in the SCN of PACAP deficient mice

Abstract

The brain’s biological clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and generates circadian rhythms in physiology and behavior. The circadian clock needs daily adjustment by light to stay synchronized (entrained) with the astronomical 24 h light/dark cycle. Light entrainment occurs via melanopsin expressing retinal ganglion cells (mRGCs) and two neurotransmitters of the retinohypothalamic tract (RHT), PACAP and glutamate, which transmit light information to the SCN neurons. In SCN neurons, light signaling involves the immediate-early genes Fos, Egr1 and the clock genes Per1 and Per2. In this study, we used PACAP deficient mice to evaluate PACAP’s role in light induced gene expression of EGR1 in SCN neurons during early (ZT17) and late (ZT23) subjective night at high (300 lux) and low (10 lux) white light exposure. We found significantly lower levels of both EGR1 mRNA and protein in the SCN in PACAP deficient mice compared to wild type mice at early subjective night (ZT17) exposed to low but not high light intensity. No difference was found between the two genotypes at late night (ZT23) at neither light intensities. In conclusion, light mediated EGR1 induction in SCN neurons at early night at low light intensities is dependent of PACAP signaling. A role of PACAP in shaping synaptic plasticity during light stimulation at night is discussed.