Neurochemistry of Mammalian Entrainment: Signal Transduction Pathways in the Suprachiasmatic Nuclei

Abstract

Neurochemical events leading to photic entrainment of circadian rhythms are reviewed. This entrainment pathway includes the retinohypothalamic tract and a glutamate-NMDA receptor (among others) interaction in the suprachiasmatic nuclei (SCN). The model we propose involves an increase in intracellular calcium levels and the activation of specific proteins in SCN neurons, including the Ca 2+ /calmodulin dependent protein kinase (CaM kinase) and phosphatase (calcineurin), other kinases (such as the cGMP-dependent protein kinase, PKG) and enzymes (nitric oxide synthase, NOS), which in turn activate specific transcription factors, in a cascade of events that is controlled both 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 occurs downstream of glutamate binding, calcium entrance, and NOS activation. We conclude that a promising way of studying the function of the circadian pacemaker is to investigate the signal transduction pathway(s) leading to changes in the SCN, including the biochemical activity of its components.