A major function of the nervous system is to maintain a relatively constant internal environment. The distinction between our external environment (i.e., the environment that we live in and that is subject to major changes, such as temperature, humidity, and food availability) and our internal environment (i.e., the environment formed by the fluids surrounding our bodily tissues and that has a very stable composition) was pointed out in 1878 by Claude Bernard (1814-1878). Later on, it was indicated by Walter Cannon (1871-1945) that the internal environment is not really constant, but rather shows limited variability. Cannon named the mechanism maintaining this limited variability homeostasis. Claude Bernard envisioned that, for optimal health, all physiologic processes in the body needed to maintain homeostasis and should be in perfect harmony with each other. This is illustrated by the fact that, for instance, during the sleep-wake cycle important elements of our physiology such as body temperature, circulating glucose, and cortisol levels show important variations but are in perfect synchrony with each other. These variations are driven by the biologic clock in interaction with hypothalamic target areas, among which is the paraventricular nucleus of the hypothalamus (PVN), a core brain structure that controls the neuroendocrine and autonomic nervous systems and thus is key for integrating central and peripheral information and implementing homeostasis. This chapter focuses on the anatomic connections between the biologic clock and the PVN to modulate homeostasis according to the daily sleep-wake rhythm. Experimental studies have revealed a highly specialized organization of the connections between the clock neurons and neuroendocrine system as well as preautonomic neurons in the PVN. These complex connections ensure a logical coordination between behavioral, endocrine, and metabolic functions that helps the organism maintain homeostasis throughout the day.
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