Melatonin: the ‘master biological clock’. Non-visual effects of light are mediated through specific retinal ganglion cells which subsequently activate SCN neurons. As a result, SCN inhibits the pineal production of melatonin during daytime through a polysynaptic pathway including paraventricular nucleus (PVN), superior cervical ganglia, and preganglionic sympathetic neurons of the lateral horn of the spinal cord. The pineal melatonin is considered the master biological clock that synchronizes the circadian rhythms of different clock genes throughout the body with different external ‘timekeepers’, such as light/dark cycles. Furthermore, the SCN-PVN network is responsible for 24-h period fluctuations of both sympathetic and parasympathetic tone, estimated with heart rate variability analysis, and for circadian oscillations of immunity and endocrine function. During inflammation, circadian rhythms of different hormones are disrupted, whereas immune cells in the periphery suppress melatonin's nocturnal surge through TNF-α and produce melatonin themselves. This extrapineal melatonin acts on a paracrine manner and exhibits both pro- and anti-inflammatory properties, depending on time phase and severity of stress. SCN, suprachiasmatic nucleus; PVN, paraventricular nucleus. Figures are reproduced from the free website: ‘The brain from top to bottom’, according to its copyleft policy (http://thebrain.mcgill.ca/flash/pop/popcopy/popcopy.html).