DOC-20241208-WA0003.

L-21 Overview of the Hypothalamus ILOs By the end of this lecture, students will be able to 1. Describe the anatomic connections between the hypothalamus and the pituitary gland 2. List the different nuclei of hypothalamus 3. Understand dif...

L-21 Overview of the Hypothalamus ILOs By the end of this lecture, students will be able to 1. Describe the anatomic connections between the hypothalamus and the pituitary gland 2. List the different nuclei of hypothalamus 3. Understand different hypothalamic functions 4. List the factors that control water intake, and outline the way they exert their effects. 5. List the temperature-regulating mechanisms, and describe the way in which they are integrated under hypothalamic control to maintain normal body temperature. 6. Discuss the pathophysiology of fever. 7. Understand role of hypothalamus on food intake 8. Describe role of hypothalamus in sleep wake cycle 9. Describe the role of hypothalamus in control of emotion The hypothalamus is the portion of the anterior end of the diencephalon that lie beneath the thalamus and forming the walls and floor of the inferior part of the third ventricle. Anatomically, the hypothalamus is part of the diencephalon, but functionally, it is part of the limbic system. It is divided into a variety of nuclei and nuclear areas that functions as an integrating center for many important homeostatic functions. The hypothalamus receives information about the internal and external environments through the input from somatic and visceral afferents and through its connections with the thalamus. The hypothalamus can be divided into functional areas of nuclei along a lateral-to-medial axis and along an anterior-to-posterior axis. Nuclei of the hypothalamus Inputs to Hypothalamus The hypothalamus receiving direct sensory inputs from the smell, taste, visual, and somatosensory systems. It also contains sensors for blood temperature, blood sugar and mineral levels, and a variety of hormones. Thus, the hypothalamus receives sensory inputs necessary to detect changes in both the internal and external environments. In addition, the hypothalamus receives inputs from the hippocampus, amygdala, and cingulate cortex. These structures form the limbic lobe of the brain, which receives highly processed sensory information from throughout the cerebral cortex. The hypothalamus has the following functions: 1. Control of endocrine functions 2. Regulation of body temperature 3. Regulation of food intake 4. serves as a major autonomic nervous system coordinating centre 5. Controls thirst and urine output 6. participates in the sleep–wake cycle 7. plays a role in emotional and behavioural patterns Endocrine functions There are neural connections between the hypothalamus and the posterior lobe of the pituitary gland and vascular connections between the hypothalamus and the anterior lobe. It controls the hormonal secretion of anterior pituitary while hormones of posterior pituitary (vasopressin and oxytocin) are synthesized by supraoptic and paraventricular nuclei of hypothalamus. (Discussed previously in Endocrine system). Regulation of Body temperature Maintenance of body core temperature within narrow limits is a major homeostatic function critical for survival. The hypothalamus is the body’s thermostat. It receives afferent information about the temperature in various regions of the body and initiates extremely complex, coordinated adjustments in heat gain and heat loss mechanisms as necessary to correct any deviations in core temperature from normal. The hypothalamus is far more sensitive to changes in blood temperature as small as 0.01°C. the hypothalamus must be informed continuously of both the core and the skin temperature by specialized thermo-receptors. The core temperature is monitored by central thermoreceptors, which are located in the hypothalamus itself as well as in the abdominal organs and great veins. Peripheral thermoreceptors monitor skin temperature throughout the body. Temperature sensors on the skin and in the hypothalamus “read” the core temperature and relay this information to the hypothalamus. The hypothalamus compares the detected core temperature to the set-point temperature. Two centers for temperature regulation are in the hypothalamus. The posterior region, activated by cold, triggers reflexes that mediate heat production and heat conservation; shivering, cutaneous vasoconstriction, hunger, increased secretion of norepinephrine and epinephrine, increased voluntary activity and decreased heat loss. The anterior region, activated by warmth, initiates reflexes that mediate heat loss as sweating, cutaneous vasodilation, increased heat loss, anorexia and inertia. A lesion in the anterior area will result in loss of these heat loss mechanisms, resulting in hyperthermia in a hot environment. A lesion in the posterior area of the hypothalamus will result in hypothermia in a cold environment Interestingly, a large bilateral lesion in the posterior area could result in poikilothermia, in which body temperature cannot be regulated and varies with the external environment (just like lizards). Fever: is an Increase in core body temperature more than 37.5 °C with an increase in the hypothalamic set point. Therefore, Core temperature will be recognized as lower than the new set-point temperature by the anterior hypothalamus. As a result, heat- generating mechanisms (e.g., shivering) will be initiated. The thermoregulatory mechanisms behave as if they were adjusted to maintain body temperature at a higher-than-normal level, that is, “as if the thermostat had been reset” to a new point above 37 °C. The temperature receptors then signal that the actual temperature is below the new set point, and the temperature-raising mechanisms are activated. This usually produces chilly sensations due to cutaneous vasoconstriction and shivering. Fever is caused by toxins from bacteria act on monocytes, macrophages, and Kupffer cells to produce cytokines that act as endogenous pyrogens (EPs). Pyrogens increased the production of IL-1. IL-1 acts on the anterior hypothalamus to increase the production of prostaglandins. Prostaglandins increase the set-point temperature, setting in motion the heat-generating mechanisms that increase body temperature and produce fever Heat stroke occurs when body temperature increases to the point of tissue damage. The normal response to increased ambient temperature (sweating) is impaired, and core temperature increases further. Regulation of food intake. Regulation of feeding involves a network of nuclei, which receive and integrate multiple peripheral anorexigenic or orexigenic signals. Lateral hypothalamus: The lateral hypothalamus has been referred to as a “hunger” or “feeding center”. neurons in the lateral hypothalamus secrete orexins, which promote feeding Stimulation of the lateral hypothalamus increases eating and drinking, whereas a lesion in the lateral area results in anorexia. the ventromedial area has been referred to as a “satiety center.” Stimulation of the ventromedial area inhibits eating, and lesions of the ventromedial area not only stimulate feeding but also decrease physical activity and alter metabolism, both of which contribute to weight gain The feeding center is chronically active, it is inhibited by satiety center when the level of glucose within neuron in satiety center is high as after meal.(Glucostatic theory) The paraventricular nucleus plays a role in mediating both anorexigenic and orexigenic signals from the arcuate and other hypothalamic nuclei and secretes hormones such as corticotropin- releasing hormone, which, like leptin, reduce food intake and increase energy metabolism. The arcuate nucleus of the hypothalamus plays a central role in control of food intake. The arcuate nucleus has two subsets of neurons that function in an opposing manner. One subset releases neuropeptide Y, and the other releases melanocortins. Neuropeptide Y (NPY), one of the most potent appetite stimulators, leads to increased food intake, thus promoting weight gain. Melanocortins, most notably melanocyte- stimulating hormone (MSH) from the hypothalamus, suppress appetite, thus leading to reduced food intake and weight loss. It was found that, neurons in the lateral portion of the arcuate nucleus mediate the anorexigenic signals from leptin, which reduce food intake and increase energy output. RELATION TO AUTONOMIC FUNCTION Stimulation of the hypothalamus produces autonomic responses, stimulation of the the lateral and posterior areas of the hypothalamus produces diffuse sympathetic discharge and increased adrenal medullary secretion, the mass sympathetic discharge seen in animals exposed to stress. However, Stimulation of the anterior (preoptic and anterior nucleus) and medial hypothalamus produces parasympathetic effects such as slowing of the heart, constriction of the pupil and salivary secretion Regulation of water balance: Regulation of water balance involves both neural and hormonal mechanisms. Stimulation of areas in the lateral hypothalamus and of osmoreceptors in the anterior region induces drinking, and nuclei in these areas can be considered a “thirst center,” whereas lesions in the lateral hypothalamus decrease water intake. Hormonal regulation occurs through specialized osmolarity-sensitive neurons in the anterior area of the hypothalamus that monitor osmolarity of the blood. Output from these neurons influences the release of ADH from the supraoptic and paraventricular nuclei, which, in turn, influence water resorption in the kidney and the production of urine. Regulation of circadian rhythms and the sleep–wake cycles The Suprachiasmatic nucleus SCN of the anterior area of the hypothalamus serves as a “master clock,” controlling both physiological and behavioral circadian rhythms, including the sleep–wake cycle, hormonal secretion, and thermoregulation. The SCN neurons have an approximately 24- hour rhythm of electrical activity. This rhythm depends on light input from the retina (retinohypothalamic tract). The retino-hypothalamic tract is a non-rod, non-cone dependent input to the SCN from a subset of retinal ganglion cells that are directly activated by light interacting with the pigment melanopsin Melatonin, which is secreted by the pineal gland in a circadian pattern. High levels secreted at night and low levels secreted during the day play a major role in the regulation of sleep and other cyclical bodily activities. Secretion of melatonin is controlled by the SCN. Neurons of the SCN send projections through the hypothalamic nuclei that influence circadian activity of endocrine secretion, visceral function, feeding, temperature regulation, and behavior Regulation of sleep is mediated by opposing actions of the anterior and posterior/lateral regions of the hypothalamus. The anterior area of the hypothalamus, particularly the preoptic area, is important for the generation of slow wave sleep (deep sleep, nonrapid eye movement), and lesions of the anterior area are known to produce insomnia in animals and humans. By contrast, the posterior area of the hypothalamus is important in wakefulness, and lesions here produce states ranging from drowsiness to coma. Histamine appears to be a major “wake promoting” neurotransmitter, and lesions in the posterior hypothalamus may produce their effect by inactivating certain subsets of histaminergic neurons. Interestingly, orexins, in addition to their effects in food intake, may have a role in promoting arousal. Deficieny in orexin neurotransmission in the lateral hypothalamus may play a role in narcolepsy. Narcolepsy is a chronic sleep disorder, , characterized by excessive daytime sleepiness in which a person experiences extreme fatigue and may fall asleep at inappropriate times, such as while at work or at school. Regulation of emotion The hypothalamus plays an important role in emotion. Lateral parts of the hypothalamus are involved in emotions such as pleasure and aggression, while the median part is associated with aversion and displeasure, The paraventricular nucleus of the hypothalamus receives inputs from various brainstem structures and from the limbic system in response to various forms of stress. The paraventricular nucleus releases corticotropin-releasing hormone, which leads to the secretion of ACTH and cortisol from the adrenal cortex, thus mediating the stress response.The limbic system receives, processes and relays emotional input to the hypothalamus. The hypothalamus through its connections with the autonomic nervous system initiates appropriate visceral responses such as changes in heart rate and blood pressure mediated by the sympathetic nervous system and associated changes in behavior.