SCN Outputs and the Hypothalamic Balance of Life

Abstract

The circadian clock in the suprachiasmatic nucleus (SCN) is composed of thousands of oscillator neurons, each dependent on the cell-autonomous action of a defined set of circadian clock genes. Still, the major question remains how these individual oscillators are organized into a biological clock producing a coherent output able to time all the different daily changes in behavior and physiology. In the present review, the authors discuss the anatomical connections and neurotransmitters used by the SCN to control the daily rhythms in hormone release. The efferent SCN projections mainly target neurons in the medial hypothalamus surrounding the SCN. The activity of these preautonomic and neuroendocrine target neurons is controlled by differentially timed waves of, among others, vasopressin, GABA, and glutamate release from SCN terminals. Together, the data on the SCN control of neuroendocrine rhythms provide clear evidence not only that the SCN consists of phenotypically (i.e., according to neurotransmitter content) different subpopulations of neurons but also that subpopulations should be distinguished (within phenotypically similar groups of neurons) based on the acrophase of their (electrical) activity. Moreover, the specialization of the SCN may go as far as a single body structure, that is, the SCN seems to contain neurons that specifically target the liver, pineal, and adrenal.

Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene

“…1) for how melatonin is released from the pineal gland [16,[20][21][22]: the circadian clock in the suprachiasmatic nucleus is more active during the day than at night. The neurons in the suprachiasmatic nucleus release γ-aminobutyric acid (GABA) to inhibit the activity of neurons in the paraventricular nucleus.…”

Cross-talks between Circadian Timing System and Cell Division Cycle Determine Cancer Biology and Therapeutics

“…The SCN can control the molecular clocks in peripheral tissues through sympathetic and parasympathetic pathways (Kalsbeek et al 2006). These clocks are also redundantly regulated and coordinated through circadian physiology Brown et al 2002;Kornmann et al 2007).…”

The circadian clock stops ticking during deep hibernation in the European hamster

“…During deep torpor, energetically expensive cellular processes such as transcription and translation are severely depressed, and physiological functions such as heart rate, respiration, immune and renal functions, and neural activity run at greatly reduced rates (1,2). The circadian system temporally coordinates internal biological processes with each other and with the environment to ensure health and survival (6)(7)(8). Circadian rhythms are temperature-compensated and run at a relatively constant pace under various temperatures (6).…”

“…Although several studies have addressed this question (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), uncertainty prevails because clock outputs rather than the core clockwork machinery were examined. In mammals, the master circadian clock is located in the suprachiasmatic nucleus of the hypothalamus (SCN) (6)(7)(8). Circadian oscillations within the SCN neurons result from the recurrent expression of so-called clock genes that interact in complex, interlocked transcription/translation feedback loops (6,7).…”