31 - Hypothalamus 1
Describe the hypothalamo-hypophyseal portal system
-Releasing hormones are produced by small neurosecretory cells located in scattered groups within the medial and ventral hypothalamus -axons of these small cells travel to a region of the underside of the hypothalamus lacking a blood-brain barrier, the median eminence, where releasing hormones are released into the hypothalamo-hypophyseal portal system of blood vessels -releasing hormones are transported through the blood to the anterior pituitary (adenohypophysis)
Describe the fornix
-a prominent fiber tract connecting the mammillary bodies with the hippocampal formation -the fornix and mammillary bodies show degenerative changes in chronic alcoholism that are believed responsible for the amnesia and confusion (Korsakoff's syndrome) seen in alcoholism
What are the tuberal nuclei?
-arucate nucleus -ventromedial nucleus -dorsomedial nucleus -tuberomammillary nucleus
What main body functions are under hypothalamic control?
-body temperature and the febrile response -food, salt, and water intake -sexual cycles, sexual orientation, and the onset of sexual milestones -circadian rhythms -sleep -body weight -stress response
What are hypothalamic signs?
-clinical signs of hypothalamic pathology generally relate to alterationsin endocrien and autonomic function (changes, in metabolism, body growth, weight and temperature, appetites, sexual behavior, developmental milestones, sleep cycles, and behavior
How does the Hypothalamus control the anterior pituitary?
-control over the anterior pituitary is exerted by 'releasing hormones' created and distributed by small neurosecretory cells in the hypothalamus -'releasing hormones' cause the anterior pituitary to release its stored 'trophic hormones' into the systemic circulation. Trophic hormones signal other endocrine organs in the body to grow and secrete their hormones
What occurs when there is damage to the optic chiasm?
-crossed optic nerve fibers in the optic chiasm serve the external (temporal) visual fields -damage to the chiasm results in bitemporal hemianopsia, or tunnel vision, and is often the first reported clinical sign of hypothalamic and pituitary tumors
What occurs when there is damage to the pituitary stalk?
-damage to the pituitary stalk can sever the hypothalamo-hypophyseal tract. Loss of vasopressin wll eventually result in the production of large volumes of weak urine by the kidneys -because the pituitary is fixed in place in the sella turcica, the infundibulum can be damaged when there is displacement of the brain in head trauma. Sudden, rapid movement of the brian can tear the pituitary stalk, severing hypothalamo-hypophyseal fibers to the posterior pititary, as well as tearing the optic chiasm away from the anterior hypothalamus, damaging it -the optic chiasm is also vulnerable to damage by pituitary tumors (more commonly) and hypothalamic tumors (less commonly)
What are the major fiber bundles of the hypothalamus?
-fornix -mammillothalamic tract -medial forebrain bundle -hypothalamo-hypophyseal tract
What are the inputs to the hypothalamus?
-in order to regulate and maintain homeostasis, the hypothalamus must receive sensory information from the body, the blood, the CSF, as well as from the external environment -hypothalamic sensory inputs can be divided into neural inputs and chemosensory inputs
How does the hypothalamus control the ANS?
-it projects directly to parasympatehtic pre-ganglionic neurons int hemidbrain (Edinger-Westphal nucleus), pons and medulla (salivaotry nuclei, nucleus ambiguus, dorsal vagal nucleus) and the sacral cord (S2-S4) -projects directly to sympathetic pre-ganglionic neurons in spinal cord levels T1-L2 including those that innervate the adrenal medulla (from T5-T11) and control epinephrine and norepinephrine release -projects to autonomic pattern generators primarily in the pons and medulla
How does the hypothalamus control the posterior pituitary?
-large cells (magnocellular neurons) in the paraventricular and supraoptic nuclei synthesize: vasopressin (ADH - controls water balance) and oxytocin (controls milk release/uterine contraction) -axons of magnocellular eurons travel in the infundibulum in the hypothalamo-hpophyseal tract to the posterior pituitary (neurohypophysis) -vasopressin and oxytocin are released from axons through fenestrated capillaried directly intot he circulation
Describe the mammillothalamic tract
-links the mammillary bodies with the anterior thalamus, an important connectio in limbic circuits
What is the paraventricular nucleus?
-located adjacent to the IIIrd ventricle in the medial hypothalamus -this is the key hypothalamic nucleus directly interfacing with the endocrine and autonomic systems -has glucose-sensitive neurons
What is the preoptic nucleus
-located immediately posterior to lamina terminalis, dorsal (and partly anterior) to the optic chiasm -integrates sensory information needed to judge deviations from set points -involved in thermoregulation, salt water intake and sleep -divided into several smaller nuclei (all have 'preoptic' in their name)
What are the sexually dimorphic nuclei (SDNs)?
-located in the anterior hypothalamus, near the medial preoptic area -these nuclei differ in their shape and cell number between men and women -a distinct form (neither male nore female) of these nuclei is found ina high proportion of gay men, suggesting they are involved in sexual orientation
What is the supraoptic nuclei?
-located laterally just above the optic tract -has osmosensitive neurons -similar to the paraventricular nucleus and an important area in humans for the release of vasopressin (antidiuretic hormone
What is the arcuate nucleus?
-located on either side of the IIIrd ventricle -one of the tuberal nuclei (along with the ventromedial, dorsomedial, and tubermammillary nuclei), located immediately deep to median eminence -involved in appetite and consumption - the key player in feeding behvaior
What is the suprachiasmatic nucleus?
-located on the midline above the optic chiasm -responsible for generating circadian rhythms for hormone release - through melatonin (governing body temperature, sexual behavior, and cycles of activity)
What is the lateral hypothalamic area (LHA)?
-stimulaing the lateral hypotahalmus causes a desire to eat. The LHA also sensd axons throughout the cerebral cortex and to the basal forebrain (Reward system) and amygdala, involved in influencing behavior
How does the hypothalamus maintain homeostasis?
-the "normal" level to which the hypothalamus strives to attain in each function it controls is termed the set point. However, the set point may e changed to meet internal (e.g. infection) and external (e.g. lack of food) challenges and is also varied according to day/night and the seasons -the basic mechanism by which the hypothalamus maintains homeotasis is comparable to a thermostat device -by constantly sampling the blood and CSF for temperature, osmolality, hormone levels, etc., and receiving CNS input from the viscera and skin, the hypothalamus can directly control the outputs of the endocrine andautonomic nervous systems (as well as more indirectly influencing behavior) to maintain set levels of function -the hypothalamus acts as both the "set point device" and the "timer" -the control devices are the ANS, endocrine, and behavrios systems on which the hypothalamus acts -the system under control is the body
How are the hypothalamic resposnes integrated?
-the ANS has in the brainstem reticular formation a number of important control centers which organize autonomic function -often called the 'head ganglion' of the ANS, the hypothalamus targets these autonomic pattern generators, allowing it to activate specific patterns of autonomic responses without activating other (for instance, when you want to lose heat, it's important to engage sweating via sympathetics, but you don't necessarily need a sudden burst of epinephrine or an increase in blood pressure) -combinations of hypothalamic centers and autonomic pattern generators allow for generation of these highly integrated and selective responses
What is the hypothalamus?
-the area of diencephalon ventral to the hypothalamic sulcus -despite its realtively small size (less than 1% of the brain in humans), it has the widest range of functions associated with any brain region, and acts as the main interface between the nervous system, and the endocrine and autonomic systems. Though rarely affected by strokes because of its rich blood supply, the hypothalamus is affected by tumors, developmental disorders, infections, alcoholism, and closed head trauma
What are the functions of the hypothalamus?
-the general function of the hypothalamus is to regulate and maintain body function (homeostasis). Integrates autonomic and endocrine functions with behavior by regulating fibe vasic physiologial needs: 1. controls blood pressure and electrolyte composition (controls drinking and salt appetities, maintains blood osmolality and vasomotor tone) 2. regulates body temperature (controls metabolic thermogenesis and behaviors that seek warmer/cooler environments) 3. controls energy metabolism (regulates feeding, digestion, and metabolis rate 4. regulates reproduction (hormonal control of mating, pregnancy, and lactation 5. controls physical and immunological responses to stress (regulates blood flow to muscle and other tissues and the secretion of adrenal stress hormone)
What are the lateral zone nuclei?
-the hypothalamus is divided by the fornix into medial and lateral zones a. lateral hypothalamic area b. tuberomamillary nucleus (only nucleus in the CNS that synthesizes histamine)
What are the medial zone nuclei?
-the hypothalamus is divided by the fornix into medial and lateral zones a. posterior nucleus b. dorsomedial nucleus c. paraventriuclar nucleus d. preoptic nucleus e. suprachiasmatic nucleus f. ventromedial nucleus g. arcuate nucleus
What are key hypothalamic landmarks?
-the hypothalamus surrounds the anterior 3/4 of the IIIrd ventricle -its anterior limit is marked by the lamina terminalis, a largely non-nervous structure tha marks the true anterior limit of the developing neural tube -its posterior limit is usually marked by a line running from the end of the mammillary bodies (two prominent swellings on the underside of the hypothalamus) to the posterior commissure -the fornix (outflow from the hippocampus) arches over the thalamus, then passes inferioly behind the anterior commissure, passing through the subsance of the hippocampus, dividing it into medial and lateral zones, and terminating in the mamillary bodies -on the inferior surface, the tuber cinereum is a hollow eminence of gray matter situated between the mamillary bodies and the optic chiasm -the median eminence is a small swelling on the tuber cinereum posterior to the funnel-shaped infundibulum (which gives rise to the pituitary stalk) -the hypothalamus consists of gray matter arranged into about 15 or so nuclei
Describe the hypothalamo-hypophyseal tract
-the infundibulum or pituitary stalk connects the underside of the hypothalamus with the pituitary gland -a bundle of axons running from the paraventricular nucleus and supraoptic nuclei to the posterior pituitary, via the pituaitary stalk, constitutes a hypothalamo-hypophyseal tract (a distinct tuberoinfundibular tract runs from dopaminergic neurons in the arcuate nucleus to the median eminence, Dopamine released at this site regulates the secretion of prolactin from the anteriro pituitary gland)
What complex behaviors is the hypothalamus involved in?
-the lateral hypothalamic area (LHA) is the majore player inthis regard, particuarly the posterior region of the LHA, which has projectiosn to: a. mesopontine cholinergic cells (acetylcholine) -> consciousness b. ventral tegmental area (dopamine) -> motivation c. locus ceruleus (norepinephreni) -> vigilance d. midbrain dorsal raphe (serotonin) -> mood e. tuberomammillary nucleus (histamine) -> wakefulness -lesions of the lateral hypothalamic area, particuarly the posterior region, tend to have profound effects on behavior/cognition
What hypothalamic nuclei connect directly with the ANS?
-the paraventricular nucleus, arcuate, and ventromedial nuclei, and lateral hypothalamus are the main hypothalamic regions connected with autonomic areas. Highly specific patterns of autonomic activity directly related to particular ongoing needs (e.g., thermoregulation) are genearted by different combinations of hypothalamic nuclei and autonomic pattern generators -axons destined for brainstem targets travel in the dorsal longitudinal fasciculus (DLF). This tract is composed of a diffuse brainstem pathway located in the PAG (periaqueductal gray matter of midbrain) and continuing caudally, comprised of descending hypothalamic axons and ascending visceral sensory axons -the hypothalamospinal pathway passes through the midbrain and pontine tegmentuma nd the lateral part of the medulla in the central tegmental tract. -hypothalamospinal axons to preganglionic neurons can influence blood pressure, sweating, vasoconstriction, and release of epinephrine and norepinephrine
Describe the "other" (besides arcuate nucleus) tuberal nuclei
-the tuberal region is the widest region of the hypothalamus, extending from the infundibulum anteriorly tot he mammillary body posteriorly 1. ventromedial nucleus: regulates satiety (desire to stop eating). Bilateral lesions produce a voracious appetite, obesity, and aggressive behavior 2. dorsomedial nucleus: poorly delineated mass of small neurons dorsal to the ventromedial nucleus. Appears to be involved in regulating complex integrative control of growth, feeding, maturation, and aspects of reproduction 3. tuberomammillary nucleus: all histaminergic axons in the CNS originate fromt he tuberomammillary nucelus of the posterior hypothalamus, with projections to almost all CNS regions. As a neurotransmitter, histamine has a broad modulatory function in the brain, with important roles in maintenance of wakefulness, sleep, and circadian rhythms
Describe the medial forebrain bundle
-this diffuse longitudinal fiber tract runs through the lateral hypothalamus, connecting the hypothalamus to the brainstem below, and with the basal forebrain, amygdala, and cerebral cortex above -damage to this bundle is thought to affect appetite as it contains lateral hypothalamic fibers -it is helpful to think of the medial forebrain bundle as a kind of "monoaminergic superhighway", as it transmits fibers from neurons using all kinds of monoamine neurotransmitters (namely serotonin, noradrenaline, dopamine, and histamine). If you want to get from the brainstem to the cortex and you're a system using monoaminergic neurotransmitters, this is one of your major pathways
What are the major outputs of the hypothalamus?
-to the anterior pituitary, the posterior pituitary, and to pre-ganglionic autonomic efferent neurons. The hypothalamus (mostly the lateral hypothalamus) also sends axons throughout the cerebral cortex and to the basal forebrain (Reward system) and amygdala, connections that are presumed to alter motivated behavior and are involved in wakefulness
What are the main sources of chemosensory input?
1. Hypothalamic chemosensory neurons: many hypothalamic neurons are themselves sensitive to circulating metabolites, e.g. glucose (glucose-sensitive neurons in paraventricular nucleus), osmolality (osmosensitive neurons inthe supraoptic nucleus), long chain fatty acids, and temperature (thermosensitive neurons inthe anterior hypothalamus -intracellular enzymes, particularly malonyl co-enzyme A, appear o be important 'sensors' of glucose and long-chain fatty acid levels in hypothalamic neurons, allowing them to change thier activity based on concentration levels 2. Hormone and steroid receptors: most hypothalamic neurons have hormone receptors. Some respond directly to hormones (e.g., ACTH) released by the pituitary (ultra-short feedback loop) or their endocrine targets. Others respond to hormones secreted by adipose tissue (leptin) or the gu (e.g., cholecystokinin 3. Circumventricular organs (CVOs): specialized structures that lack a blood-brain barrier. Thought to 'sample' blood and CSF and transmit information on solute concentrations to the hypothalamus.
What are the main sources of neural inputs that convey information from the internal and external environment to the hypothalamus?
1. The retina: a select population of photo-sensitive retinal ganglion cells (not rods or cones) send axons to the suprachiasmatic nucleus 2. the olfactory system: these are mostly indirect inputs but are still prominent in humans 3. spinohypothalamic inputs: somatosensory information (mostly thermal and some nociceptive) from the skin and deep tissues is conveyed directly by a component of the spinothalamic system, the spinohypothalamic pathway (essentially, the ascending spinothalamic tract sends collaterals to the hypothalamus); additional information arrives indirectly through the reticular formation 4. viscerosensroy inputs: sensory information from the GI tract, the liver (a large input) and abdominal viscera, from baroreceptors (blood pressure) and chemoreceptors (pCO2) in the heart and carotids reaches the hypothalamus via axons arising in the nucleus of the solitary tract (NTS) in the dorsal medulla. -taste information also reaches the hypothalamus via the NTS and parabrahcial nucleus -afferents associated with the sympathetic system reach the hypothalamus via the spinohypothalamic pathway 5. additional sources of input include the prefrontal cortex, the insula, the amygdala, and the hippocampal formation (to the mammillary bodies)
What are the 3 important circumventricular organs (CVOs)?
1. subfornical organ (SFO) -sensitive to CSF angiotensin II 2. vascular organ of the lamina terminalis (VOLT) -sensitive to serum osmolality 3. median eminence (ME) - apart from its role in hypothalamic control of anterior pituitary hormone secretion, the median eminence is thought to be the mainsite where hormones, peptides, and other signaling molecules cross the blood brain barrier to reach the hypothalamus
What are the medial and lateral nuclei?
Medial: a. paraventricular nucleus b. dorsomedial nucleus c. ventromedial nucleus d. arcuate nucleus Lateral: a. tuberomamillary nucleus
What are the posterior nuclei?
a. Posterior nucleus b. tuberomamillary nucleus c. lateral mamillary nucleus d. medial mamillary nucleus
