Figure 9.

Schematic diagram summarizing SCN cellular responses to circadian and arousal-promoting cues in nocturnal rodents. A, Throughout the subjective day, electrical activity and inhibitory output from the SCN is high (thick blue line), with orexinergic cells in the lateral hypothalamus (LH) minimally active, providing nominal/no presynaptic signal (green arrow) to liberate GABA in the SCN to suppress activity of Per1-EGFP neurons. At this circadian phase, the inhibitory signal from IGL-NPY cells to the SCN is also at a nadir (thin red line) due to low/no orexinergic excitatory signal (thin green arrow) to the IGL. B, During the night, electrical activity and inhibitory output from the SCN is low (thin blue line), with orexinergic cells showing elevated electrical activity, providing strong excitatory input to IGL-NPY cells (thick green arrow) and large postsynaptic direct inhibitory input to SCN Per1-EGFP cells (thick red line). C, During daytime, arousal-promoting stimuli activate orexin cells, providing increased orexinergic signaling to the SCN (thick green line). This initially elevates GABA release in the SCN which then suppresses SCN electrical activity. Increased orexinergic signaling also activates IGL-NPY cells (thick green arrow), which also provides further suppressive signal to the SCN (thick red line). In the SCN, orexin facilitates NPY's inhibitory actions by enhancing GABA signaling. The width of the arrows (excitatory signal) and T-bars (inhibitory signal) indicates the level of excitation or inhibition, respectively. D, Circadian variation in SCN (blue line) and orexin (orange line) cellular activity, and the effects of daytime arousal-promoting stimuli on this activation (broken lines; Marston et al., 2008; van Oosterhout et al., 2012).