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The hypothalamus plays three critical roles in the actions of the nervous system. First, it serves as the “head ganglion” of the autonomic nervous system, as described in the preceding chapter; second, it is a circadian and seasonal clock for behavioral and sleep–wake functions, as considered in Chap. 18 on sleep; third, it provides neural control of the endocrine system, as discussed in this chapter. The hypothalamus integrates these systems with one another as well as with neocortical, limbic, and spinal networks. Ultimately, the hypothalamus maintains complex homeostatic functions and participates in the substructure of emotion and affective behavior.

Hypothalamic nuclei serve pivotal roles in the maintenance of homeostasis by virtue of having rich bidirectional interconnectivity with multiple brain regions, including multiple sources of afferent input and autonomic, endocrine, and neuroendocrine motor outputs (Stern). For example, visceroceptive inputs arising mostly from the brainstem convey information about a variety of homeostatic perturbations, then eliciting complex patterns of neurosecretory and autonomic hypothalamic output that act upon peripheral tissues to re-establish bodily homeostasis.

The concept of neurosecretion probably had its origins in the observations of Speidel, who noted in 1919 that some hypothalamic neurons had the morphologic characteristics of glandular cells. That idea, which is now viewed as a fundamental part of the science of endocrinology, was so novel that it was rejected by most biologists at the time. The expansion of knowledge of neuroendocrinology during the past century stands as one of the significant achievements in neurobiology. It is now well established that neurons, in addition to transmitting electrical impulses, can synthesize and secrete complex molecules locally and into the systemic circulation and that these molecules are capable of stimulating or inhibiting endocrine, renal, and vascular cells at distant sites.

Following the work of Spiedel, von Euler and Gaddum made the seminal observation in 1931 that peptides secreted by neurons in the central and peripheral nervous systems were also secreted by glandular cells of the pancreas, intestines, and heart. They isolated a substance from the intestines that was capable of acting on smooth muscle and called it “P” (for “powder”). It was not until some 35 years later that Leeman and associates purified an 11-amnio-acid peptide that is now called substance P (see Aronin et al). Then followed the discovery of six hypothalamic mediators of anterior pituitary hormone secretion: thyrotropin-releasing hormone (TRH), somatostatin, gonadotropin-releasing hormone (GnRH), corticotropin-releasing hormone (CRH), and hormone-releasing hormone (GHRH). In addition, dopamine’s action as an inhibitor of pituitary hormone secretion was established and elucidated. Subsequently, a number of other neuropeptides were discovered, including enkephalin, neuropeptide Y, and orexin, as discussed in Chap. 18.


Anatomic Features

The hypothalamus lies on each side of the third ventricle and extends across the floor of the ventricle. It is bounded posteriorly by the mammillary bodies, anteriorly by the ...

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