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The hypothalamus, which serves autonomic, appetitive, and regulatory functions, lies below and in front of the thalamus; it forms the floor and lower walls of the third ventricle (see Fig 9–1). External landmarks of the hypothalamus are the optic chiasm; the tuber cinereum, with its infundibulum extending to the posterior lobe of the hypophysis; and the mammillary bodies lying between the cerebral peduncles (Fig 9–6).
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The hypothalamus can be divided into an anterior portion, the chiasmatic region, including the lamina terminalis; the central hypothalamus, including the tuber cinereum and the infundibulum (the stalk connecting the pituitary to the hypothalamus); and the posterior portion, the mammillary area (Fig 9–7).
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The right and left sides of the hypothalamus each have a medial hypothalamic area that contains many nuclei and a lateral hypothalamic area that contains fiber systems (eg, the medial forebrain bundle) and diffuse lateral nuclei.
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Medial Hypothalamic Nuclei
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Each half of the medial hypothalamus can be divided into three parts (Fig 9–8): the supraoptic portion, which is farthest anterior and contains the supraoptic, suprachiasmatic, and paraventricular nuclei; the tuberal portion, which lies behind the supraoptic portion and contains the ventromedial, dorsomedial, and arcuate nuclei in addition to the median eminence; and the mammillary portion, which is the farthest posterior and contains the posterior nucleus and several mammillary nuclei. The preoptic area lies anterior to the hypothalamus, between the optic chiasm and the anterior commissure.
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CLINICAL CORRELATIONS
The thalamic syndrome is characterized by immediate hemianesthesia, with the threshold of sensitivity to pinprick, heat, and cold rising later. When a sensation, sometimes referred to as thalamic hyperpathia, is felt, it can be disagreeable and unpleasant. The syndrome usually appears during recovery from a thalamic infarct; rarely, persistent burning or boring pain can occur (thalamic pain).
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Consistent with its autonomic and regulatory functions, the hypothalamus receives inputs from limbic structures, thalamus and cortex, visceral and somatic afferents, and sensors such as osmoreceptors, which permit it to monitor the circulation.
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Afferent connections to the hypothalamus include part of the medial forebrain bundle, which sends fibers to the hypothalamus from nuclei in the septal region, parolfactory area, and corpus striatum; thalamohypothalamic fibers from the medial and midline thalamic nuclei; and the fornix, which brings fibers from the hippocampus to the mammillary bodies. These connections include the stria terminalis, which brings fibers from the amygdala; pallidohypothalamic fibers, which lead from the lentiform nucleus to the ventromedial hypothalamic nucleus; and the inferior mammillary peduncle, which sends fibers from the tegmentum of the midbrain. A small number of ganglion cells from throughout the retina (less than 1%) send axons that provide visual input to the suprachiasmatic nucleus via the retinohypothalamic tract. These and other connections are shown in Table 9–2.
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Affective and emotional inputs from the prefrontal cortex reach the hypothalamus via a polysynaptic pathway that passes through the dorsomedial nuclei of the thalamus. In addition, visceral information from the vagal sensory nuclei, gustatory messages from the nucleus solitarius, and somatic afferent messages from the genitalia and nipples are relayed to the hypothalamus.
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Efferent tracts from the hypothalamus include the hypothalamohypophyseal tract, which runs from the supraoptic and paraventricular nuclei to the neurohypophysis (see the next paragraph); the mamillotegmental tract (part of the medial forebrain bundle) going to the tegmentum; and the mamillothalamic tract (tract of Vicq d'Azyr), from the mammillary nuclei to the anterior thalamic nuclei. There are also the periventricular system, including the dorsal fasciculus to the lower brain levels; the tuberohypophyseal tract, which goes from the tuberal portion of the hypothalamus to the posterior pituitary; and fibers from the septal region, by way of the fornix, to the hippocampus (see Chapter 19).
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There are rich connections between the hypothalamus and the pituitary gland. The pituitary has two major lobes: the posterior pituitary (neurohypophysis) and anterior pituitary (adenohypophysis). Neurons in the supraoptic and paraventricular nuclei send axons, via the hypothalamohypophyseal tract, to the neurohypophysis. These axons transport Herring bodies, which contain precursors of the hormones oxytocin and vasopressin (also known as antidiuretic hormones, or ADHs) to the posterior pituitary. Oxytocin and vasopressin are released from axon endings in the posterior pituitary and are then taken up by a rich network of vessels that transports them to the general circulation (Figs 9–8 and 9–9).
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Neurons in other hypothalamic nuclei regulate the adenohypophysis via the production of a group of hypophyseotropic hormones that control the secretion of anterior pituitary hormones (Fig 9–10). The hypophyseotropic hormones include releasing factors and inhibitory hormones, which, respectively, stimulate or inhibit the release of various anterior pituitary hormones.
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Communication between the hypothalamus and adenohypophysis involves a vascular circuit (the portal hypophyseal system) that carries hypophyseotropic hormones from the hypothalamus to the adenohypophysis. After their synthesis in the cell bodies of neurons located in the hypothalamic nuclei, these hormones are transported along relatively short axons that terminate in the median eminence and pituitary stalk. Here they are released and taken up by capillaries of the portal hypophyseal circulation. The portal hypophyseal vessels form a plexus of capillaries and veins that carries the hypophyseotropic hormones from the hypothalamus to the anterior pituitary. After delivery from the portal hypophyseal vessels to sinusoids in the anterior pituitary, the hypophyseotropic hormones bathe the pituitary cells and control the release of pituitary hormones. These pituitary hormones, in turn, play important regulatory roles throughout the body (Fig 9–11).
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Although the hypothalamus is small (weighing 4 g, or about 0.3% of the total brain weight), it has important regulatory functions, as outlined in Table 9–3.
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A tonically active feeding center in the lateral hypothalamus evokes eating behavior. A satiety center in the ventromedial nucleus stops hunger and inhibits the feeding center when a high blood glucose level is reached after food intake. Damage to the feeding center leads to anorexia (loss of appetite) and severe loss of body weight; lesions of the satiety center lead to hyperphagia (overeating) and obesity.
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B. Autonomic Function
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Although anatomically discrete centers have not been identified, the posterolateral and dorsomedial areas of the hypothalamus function as a sympathetic (catecholamine) activating region, whereas an anterior area functions as a parasympathetic activating region.
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When some regions of the hypothalamus are appropriately stimulated, they evoke autonomic responses that result in loss, conservation, or production of body heat. A fall in body temperature, for example, causes vasoconstriction, which conserves heat, and shivering, which produces heat. A rise in body temperature results in sweating and cutaneous vasodilation. Normally, the hypothalamic set point, or thermostat, lies just below 37°C of body temperature. A higher temperature, or fever, is the result of a change in the set point, for example, by pyrogens in the blood.
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Hypothalamic influence on vasopressin secretion within the posterior pituitary is activated by osmoreceptors within the hypothalamus, particularly in neurons within a "thirst center" located near the supraoptic nucleus. The osmoreceptors are stimulated by changes in blood osmolarity. Their activation results in the generation of bursts of action potentials in neurons of the supraoptic nucleus; these action potentials travel along the axons of these neurons, to their terminals within the neurohypophysis, where they trigger the release of vasopressin. Pain, stress, and certain emotional states also stimulate vasopressin secretion. Lack of secretion of vasopressin caused by hypothalamic or pituitary lesions can result in diabetes insipidus, which is characterized by polyuria (increased urine excretion) and polydipsia (increased thirst).
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E. Anterior Pituitary Function
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The hypothalamus exerts a direct influence on secretions of the anterior pituitary and an indirect influence on secretions of other endocrine glands by releasing or inhibiting hormones carried by the pituitary portal vessels (see Fig 9–9). It thus regulates many endocrine functions, including reproduction, sexual behavior, thyroid and adrenal cortex secretions, and growth.
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Many body functions (eg, temperature, corticosteroid levels, oxygen consumption) are cyclically influenced by light intensity changes that have a circadian (day-to-day) rhythm. Within the hypothalamus, a specific cell group, the suprachiasmatic nucleus, functions as an intrinsic clock. Within these cells, there are "clock genes," including two genes called clock and per, that turn on and off with a circadian, once-per-day, rhythm (Fig 9–12). Thus, cells within the suprachiasmatic nucleus show circadian rhythms in metabolic and electrical activity, and in neurotransmitter synthesis, and appear to keep the rest of the brain on a day–night cycle. A retinosuprachiasmatic pathway carries information about the light intensity and can "entrain" the suprachiasmatic clock in order to synchronize its activity with environmental events (eg, the light–dark day–night cycle). In the absence of any sensory input, the suprachiasmatic nucleus itself can function as an independent clock with a period of about 25 hours per cycle; lesions in this nucleus cause the loss of all circadian cycles.
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G. Expression of Emotion
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The hypothalamus is involved in the expression of rage, fear, aversion, sexual behavior, and pleasure. Patterns of expression and behavior are subject to limbic system influence and, in part, to changes in visceral system function (see Chapters 19 and 20).