Resetting the Biological Clock: Mediation of Nocturnal CREB Phosphorylation via Light, Glutamate, and Nitric Oxide

• DOI: 10.1523/jneurosci.17-02-00667.1997
• Publication Date: 2018-04-02T23:25:56Z
• Authors: Jian M. Ding; Lia E. Faiman; William J. Hurst; Liana R. Kuriashkina; Martha U. Gillette
• Keywords: 0301 basic medicine; N-Methylaspartate; Time Factors; Light; NADPH Dehydrogenase; Glutamic Acid; Nerve Tissue Proteins; Rats, Inbred Strains; Nitric Oxide; Circadian Rhythm; Rats; 03 medical and health sciences; 2-Amino-5-phosphonovalerate; Gene Expression Regulation; Animals; Suprachiasmatic Nucleus; Enzyme Inhibitors; Nitric Oxide Synthase; Phosphorylation; Cyclic AMP Response Element-Binding Protein; Protein Processing, Post-Translational; Photic Stimulation

Synchronization between the environmental lighting cycle and biological clock in suprachiasmatic nucleus (SCN) is correlated with phosphorylation of Ca2+/cAMP response element binding protein (CREB) at transcriptional activating site Ser133. Mechanisms mediating formation phospho-CREB (P-CREB) their relation to resetting are unknown. To address these issues, we probed signaling pathway light P-CREB. Nocturnal rapidly transiently induced P-CREB-like immunoreactivity (P-CREB-lir) rat SCN. Glutamate (Glu) or nitric oxide (NO) donor administration vitro also P-CREB-lir SCN neurons only during subjective night. Clock-controlled sensitivity phase by light. Glu, NO similarly restricted The effects NMDA synthase (NOS) antagonists on Glu-mediated induction paralleled inhibition shifting. Significantly, among which was were NADPH-diaphorase-positive SCN's retinorecipient area. Glu treatment increased intensity a 43 kDa band recognized anti-P-CREB antibodies night but not day, whereas anti-alpha CREB-lir this remained constant day. Inhibition NOS stimulation diminished anti-P-CREB-lir band. Together, data couple nocturnal light, receptor activation CREB transduction brief retina into molecular changes resulting clock.