Fig. 2.

Photic- and non-photic-responsive MAPK signaling pathways in the brain. In photic circadian clock entrainment, the neurotransmitters glutamate and PACAP are released onto SCN neurons via the eye and RHT. The activation of NMDA and Pac1 receptors in turn results in the activation of Ras and heterotrimeric G proteins, which successively activate ERK and CREB. Non-photic stimulation by SD, ECT, or DBS leads to the activation of adenosine A₁ receptors, which leads to the activation of ERK and CREB. Phosphorylated CREB is translocated to the nucleus and activates the transcription of immediate-early genes, including Per1. SD, sleep deprivation; ECT, electroconvulsive therapy; DBS, deep brain stimulation; P, phosphorylation; ER, endoplasmic reticulum; TSS, transcription start site.