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Light and circadian rhythmicity regulate MAP kinase activation in the suprachiasmatic nuclei

Abstract

Although the circadian time-keeping properties of the suprachiasmatic nuclei (SCN) require gene expression, little is known about the signal transduction pathways that initiate transcription. Here we report that a brief exposure to light during the subjective night, but not during the subjective day, activates the p44/42 mitogen-activated protein kinase (MAPK) signaling cascade in the SCN. In addition, MAPK stimulation activates CREB (cAMP response element binding protein), indicating that potential downstream transcription factors are stimulated by the MAPK pathway in the SCN. We also observed striking circadian variations in MAPK activity within the SCN, suggesting that the MAPK cascade is involved in clock rhythmicity.

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Figure 1: Photic stimulation during subjective night triggers activation of the MAPK signaling cascade.
Figure 2: Five-minute photic stimulation elicits ERK activation.
Figure 3: Photic stimulation during subjective day (CT 6) does not elicit MAPK activation.
Figure 4: Photic stimulation results in nuclear co-localization of P-ERK and P-CREB in the SCN.
Figure 5: Glutamate triggers ERK activation in SCN slice and SCN-enriched primary neuron cultures.
Figure 6: Circadian variations in the activation state of ERK.
Figure 7: Levels of ERK did not vary significantly as a function of circadian time.

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Acknowledgements

We thank S. Poser and J. Athos for comments on the manuscript. Confocal microscopy and image analysis was done in the W. M. Keck Center for Neural Signaling, University of Washington. This research was supported by National Institutes of Health grant NS 20498.

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Correspondence to Daniel R. Storm.

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Obrietan, K., Impey, S. & Storm, D. Light and circadian rhythmicity regulate MAP kinase activation in the suprachiasmatic nuclei. Nat Neurosci 1, 693–700 (1998). https://doi.org/10.1038/3695

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