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1

function of hypothalamus

coordinates endocrine, autonomic, and somatic motor responses in order to achieve homeostasis in a broad range of physiological parameters including body temperature, blood pressure, fluid and electrolyte balance, body weight.

2

Describe three regions of hypothalamus

anterior (supraoptic) = above the optic chiasm; medial (tuberal) = above the pituitary; and posterior (mammillary) = above and including the mammillary bodies

3

1.       Describe the location of the major nuclei of the hypothalamus.

Anterior: lateral and medial preoptic nuclei, suprachiasmatic nucleus. Medial: paraventricular nucleus, dorsomedial nucleus, anterior nucleus, ventromedial nucleus, supraoptic nucleus, arcuate nucleus. Posterior: mamillary body

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2.       Describe the pathways connecting the hypothalamus with the autonomic system

hypothalamus neurons innvervate preganglionic neurons of the sympathetic and parasympathetic nervous systems. The preganglionic neurons of the SNS are located in the intermediolateral column of the thoracic and upper three lumbar segments of the spinal cord (T1-L3), and the preganglionic neurons of the PSNS are located in brainstem nuclei and in the sacral spinal cord. Pre-ganglionic neurons synapse on post-gangloinic neurons that innervate smmoth muscle, cardiac muscle, glands

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2.       Describe the pathways connecting the hypothalamus with the somatic motor systems

Hypothalamic neurons innervate upper motor neurons in the brainstem reticular formation which then project to the lower motor neurons that innervate skeletal muscle. By coordinating activity in these neurons with actions of autonomic neurons, the hypothalamus can organize and initiate complex activities that require both somatic and autonomic responses such as vomiting,

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efferent pathways from hypothalamus to autonomic and somatic nervous systems

a. Dorsal longitudinal fasiculus: to autonomic nuclei in the brainstem reticular system and spinal cord. b. Medial forebrain bundle: to brainstem reticular formation. c. Mammillotegmental tract: from the mammillary bodies to the midbrain reticular formation (tegmentum)

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2.       Describe the pathways connecting the hypothalamus with the endocrine system

The hypothalamus regulates hormone release from both the anterior and posterior lobes of the pituitary

8

hypothalamic control of posterior pituitary

Direct: Vasopressin (ADH) and oxytocin aare synthesized by neurons in supraoptic and paraventricular nuclei in hypothalamus. The hormones are transported down the axons of these neurons to the posterior pituitary where they are stored until released by action potentials directly into the general circulation

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function of vasopressin

acts on the kidneys to increase water reabsorption

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function of oxytocin

causes constriction of smooth muscle in the uterus and mammary glands and thereby plays important roles in parturition and lactation

11

hypothalamic control of anterior pituitary

Indirect: The hypothalamus synthesizes and releases hormones (CRH, GnRH, TRH, etc) into the hypothalamo-pituitary portal circulation which are then carried to endocrine cells of anterior pituitary and control release of hormones by glandular cells of anterior pituitary (LH, GH, ACTH, PRL, TSH, FSH).

12

Describe afferent pathways to hypothalamus

Ascending information from visceral receptors (e.g. baroreceptors, gastric or cervical stretch, etc.) is relayed to neurons in the brainstem reticular formation. Axons from these reticular neurons then ascend to the hypothalamus in the dorsal longitudinal fasciculus and medial forebrain bundle. These are called reciprocal pathways b/c they also carry efferent projections from hypothalamus

13

Describe humoral afferents to hypothalamus

The hypothalamus also monitors humoral signals from the periphery that provide important information for maintaining homeostasis. Regions in the hypothalamus and preoptic area lack a blood-brain barrier. These areas are called circumventricular organs

14

List the circumventricular organs, there locations

organum vasculosum of the lamina terminalis (OVLT) located at the front of the bottom of the third ventricle, the subfornical organ (SFO) located at the top of the third ventricle, the median eminence located at the bottom of the third ventricle, and the posterior pituitary.

15

How do circumventricular organs allow humoral afferent connection to hypothalamus

These regions contain fenestrated capillaries that allow peptides and polypeptides that are excluded from other brain regions to pass from the blood into the brain. For example, angiotensin II produced by the peripheral renin-angiotensin system induces thirst by acting on neurons in the SFO, and leptin (a hormone produced by white adipocytes) accesses hypothalamic neurons involved in regulation of food intake via the median eminence

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2.       Describe the pathways connecting the hypothalamus with the limbic system.

The following reciprocal pathways carry both afferent and efferent axons: a. Fornix: connections between hippocampus and mamillary bodies b. Stria terminalis: connections between amygdala and the anterior and tuberal regions of hypothalamus. c. Medial forebrain bundle: connections between hypothalamus and prefrontal cortex and septum. Additionally, the mamillothalamic tract is an efferent pathway connecting the mammillary bodies with the anterior thalamus

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8.       Describe the role of the hypothalamus in emotional and motivated responses. What is ‘sham rage’?

hypothalamus is disconnected from higher brain areas (decorticate) but the hypothalamic connections to the brainstem and spinal cord remain intact. This produces animals that are extremely aggressive and irritable. The responses are short lived and poorly directed, ocur in response to inappropriate stimuli. disconnecting the the hypothalamus from the brainstem abolishes sham rage. This indicates that the hypothalamus can initiate the somatic and autonomic reactions to sensory input even in the absence of cortical input

18

which region of hypothalamus controls heating and cooling

Thermoreceptors in preoptic Anterior hypothalamus senses when body is too hot and increases firing and triggers cooling. Posterior hypothalamus senses when body is too cold and generates heat. There are also cells in the POAH which are active at normal body temp and inhibit cells of posterior hypothalamus.

19

Describe heat production as by product of metabolism

For a typical 70 kg man the resting (basal) rate of metabolic heat production amounts to 80 kcal/hr. The basal metabolic rate is influenced by thyroxin; increases in thyroxin increase basal heat production and decreases reduce heat production. Thyroxin stimulates both catabolic and anabolic metabolic pathways.

20

how does exercise and shivering affect basal heat production

Intense exercise can generate 400-600 kcal/hr, thereby increasing the resting rate of heat production more than 7-fold! Shivering increases basal heat production two-fold. Although shivering is involuntary, since it involves contraction of skeletal muscle, it is under control of the somatic motor system rather than the autonomic nervous system.

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non shivering thermogenesis

Infants and small-bodied cold-exposed mammals, both of which possess significant brown fat deposits, can increase heat production by increasing the catabolic activity of this tissue. Norepinephrine release onto brown fat by sympathetic fibers signals activation of thermogenin or uncoupling protein 1 (UCP1). This is a H ion channel in inner mitochondria membrane in brown fat cells, when opened it dissipates proton motive force as heat without producing ATP.

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mechanisms of cooling

1. blood flow (sympathetic vasomotor control)- more blood flow means more cooling. 2. sweating (sympathetic control)

23

Fever- induced by what?

Fever is a regulated increase in body temperature (hyperthermia). It is induced by the actions of pyrogens (fever producing agents) to increase the "set-point" of the thermoregulatory system. Pyrogens have a direct effect on the POAH by decreasing activity of thermoreceptors, activating thermogenic responses (vasoconstriction, shivering).

24

Direct mechanism of fever

Fever is produced by the actions on the POAH of one or more of the cytokines (interleukin 1 [IL-1], interleukin 6 [IL-6], tissue necrosis factor [TNF] and interferon). IL-1 can affect the thermoreceptors in the POAH by acting at a region in the hypothalamus that lacks a blood brain barrier, the OVLT (organumvasculosum of the lamina terminalis). It induces the endothelial cells in this region to produce prostaglandin E2. PGE2 then diffuses into the adjacent POAH and decreases the activity of the thermoreceptors, thereby resetting the hypothalamic temperature "set point" to a higher level

25

What are the somatic, endocrin and sensory componnets of water balance integrated by hypothalamus

a. Somatic reactions – drinking (motivated behavior; swallowing) b. Endocrine reactions--release of antidiuretic hormone (ADH, vasopressin c. Sensory input -- dryness of mouth; hypothalamic "osmoreceptors"; cardiovascular volume receptors (left atrium, aortic arch; carotid sinus monitors blood pressure)

26

Functions of hypothalamus in water balance

a. Osmoreception -- Anterior hypothalamus: Organum vasculosum of lamina terminalis (OVLT) and subfornical organ (SFO) monitor plasma osmolality for both thirst and ADH release. b. ADH synthesis – supraoptic (SON) and paraventricular nuclei. c. Temperature – osmoreceptive areas (OVLT and SON) are also temperature sensitive providing a mechanism to integrate body water and temperature homeostasis

27

hypothalamic functions in body weight

a. Ventromedial nucleus -- satiety center 1). Lesion -- increases food intake, marked obesity, heightened sensitivity to food (both noxious and palatable) 2). Stimulation -- inhibits urge to eat 3). Overlaps with emotional control mechanisms. b. Lateral hypothalamus -- hunger or feeding center 1). Lesions -- anorexia, starvation, decreased responsivity to food 2). Stimulation -- induces food intake. c. Paraventricular nucleus 1). Lesions -- similar to ventromedial nucleus d. Arcuate nucleus – monitors peripheral hormone levels.

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Hypothalamus and circadian rhythms

The primary circadian clock in the body is located in the suprachiasmatic nucleus (SCN) of the hypothalamus which receives direct innervation from retina. Peripheral clocks are located in organs throughout the body and are entrained by the central clock and other cues such as food