Neurochemistry of mammalian entrainment: Signal transduction pathways in the suprachiasmatic nuclei

Neurochemical events leading to photic entrainment of circadian rhythms are reviewed. This entrainment pathway includes the retinohypothalamic tract a nd a glutamate-NMDA receptor (among others) interaction in the suprachiasma tic nuclei (SCN). The model we propose involves an increase in intracellula r calcium levels and the activation of specific proteins in SCN neurons, in cluding the Ca2+/calmodulin dependent protein kinase (CaM kinase) and phosp hatase (calcineurin), other kinases (such as the cGMP-dependent protein kin ase, PKG) and enzymes (nitric oxide synthase, NOS), which in turn activate specific transcription factors, in a cascade of events that is controlled b oth by light and by the circadian clock itself. Although the step at which the circadian gating of this process occurs is unknown, we propose it occur s downstream of glutamate binding, calcium entrance, and NOS activation. We conclude that a promising way of studying the function of the circadian pa cemaker is to investigate the signal transduction pathway(s) leading to cha nges in the SCN, including the biochemical activity of its components.