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.
Highlights
Circadian rhythms in physiology and behaviour are in mammals generated from the suprachiasmatic nucleus (SCN), located in the ventral hypothalamus
In both genotypes Egr1 mRNA was significantly induced in the SCN after light stimulation at early night with 300 lux compared to the controls (Fig 3A)
We found that PACAP signaling via the retinohypothalamic tract (RHT) is involved in light induction of EGR1 gene expression within neurons of the SCN
Summary
Circadian rhythms in physiology and behaviour are in mammals generated from the suprachiasmatic nucleus (SCN), located in the ventral hypothalamus. The SCN consists of approximately 20,000 neurons and most of these neurons express a circadian clock, which is synchronized by internal neuronal signals to a coherent rhythm close to 24 h cycles [1, 2]. The molecular machinery of the biological clock consists of a group of clock genes, which by complex feedback interactions between the clock proteins drive circadian rhythmicity within neurons of the SCN (Mohawk and Takahashi, 2011; Mohawk et al, 2012). The endogenous period length of the circadian clock deviates slightly from 24 h and neurons of the SCN are daily synchronized (entrained) to the astronomical day by light, which is the most important “zeitgeber” for entrainment (Golombek and Rosenstein, 2010). Light information for entrainment is transmitted from intrinsically photosensitive retinal ganglion cells
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