Review of Medical Physiology - William F. Ganong 2002

Functions of the Nervous System
Central Regulation of Visceral Functions
Hypothalamus - Relation to Cyclic Processes

The vital Functions of most (if not all) living organisms undergo rhythmic oscillations with a period of approximately 24 hours, known as circadian rhythms (from the Latin circa, meaning approximately, and dies, meaning day). Under normal conditions, these functions are synchronized with the light-dark cycle. In animals (as well as humans), regulated processes include rhythms in ACTH secretion (see Fig. 20-18) and melatonin secretion (see Fig. 24-13), Sleep-wake cycles, and cyclic variations in BODY Temperature AND behavioral patterns in laboratory animals. Most of these rhythms are governed by the suprachiasmatic nuclei (SCN), which are located on either side just above the optic chiasm (see Fig. 14-2).

CNS Neurons retain their intrinsic rhythmic activity even when isolated from the Brain and cultured in vitro. Furthermore, transplantation of CNS tissue into animals with ablated SCN restores their circadian rhythms. It remains unclear whether this restorative effect is mediated humorally or through The formation of new neural connections established by the graft's processes. Endocrine and Neural Pathways extending from the Hypothalamus to various PARTS OF THE body regulate these rhythms, including the nocturnal release of melatonin, which acts as a systemic time cue (see Chapter 24).

Biological clocks in plants, insects, and mammals share striking similarities. In mammals, CNS Cells contain a clock composed of at least six Proteins. PER proteins are synthesized and subsequently phosphorylated by Kinases. Phosphorylated PER proteins inhibit their own synthesis, thereby driving a regular circadian rhythm.

Afferent signals entraining circadian rhythms to the light-dark cycle originate in the eyes (enucleation abolishes this response) via retinohypothalamic tracts that project directly from the optic chiasm to the CNS. However, in mice lacking functional rods and cones, these afferent signals persist, indicating the involvement of alternative photoreceptors. Cryptochrypts are photopigment molecules that mediate circadian rhythms in plants and insects, while mammals possess two homologous molecules, CRY 1 and CRY 2. Although they likely function as photoreceptors, they account for only a component of the clock mechanism; consequently, the search for the structures responsible for photoreception is ongoing.

Interestingly, bright light can exert a positive, negative, or neutral effect on the human sleep-wake cycle depending on the time of day. During the daytime, light has no effect; however, immediately after onset of darkness, exposure to bright light delays sleep onset, whereas exposure just before dawn advances the onset of the subsequent sleep period. Melatonin injections produce a similar effect. In experimental animals, light exposure activates immediate-early genes (see Chapter 1) in neurons of the suprachiasmatic nuclei, but exclusively during the phase of the circadian cycle when light is capable of exerting an effect. Daytime stimulation is ineffective. The CNS also receives robust serotonergic input from the raphe nuclei; however, the precise role of these nuclei in rhythm regulation remains unknown.