Light-induced Changes in the Suprachiasmatic Nucleus Transcriptome Regulated by the ERK/MAPK Pathway

The mammalian master circadian pacemaker within the suprachiasmatic nucleus (SCN) maintains tight entrainment to the 24 hr light/dark cycle via a sophisticated clock-gated rhythm in the responsiveness of the oscillator to light. Intriguingly, entrainment is not merely a passive response, instead the internal oscillator responds and adjust its own timing to entrainment signals discriminating the time of day. For example, exposure to brief light pulses in the first and final hours of the subjective generate circadian phase delays and advances respectively; whereas similar photic pulses during the subjective day does not modify the phase. A central event in this light entrainment process appears to be the rapid induction of gene expression via the ERK/MAPK pathway. We used microarray-based expression profiling of the suprachiasmatic nucleus to examine the role of MAPK signaling in the light-evoked transcriptional response. We focused on three circadian timepoints that define the unique, clock-time delimited response properties of the SCN to light: the subjective day, early subjective night, and late subjective night. To profile the light-evoked, clock-gated, transcriptional profile in the suprachiasmatic nucleus, mice were infused with U0126 (or DMSO as vehicle) and exposed to light (or sham light-treated) at the three noted time points: the subjective day (CT4), early subjective night (CT15, and late subjective night (CT22) After light exposure, animals were returned to darkness for 50 minutes (corresponding to 1 hour after the onset of light), then sacrificed and total SCN RNA was extracted and prepared for microarray analysis. For each individual sample, the SCN from two different mice under the same treatment were pool togetther. Each grouop was run by tryplicate.