HYPOTHALAMUS.pptx

development, anatomy, functions, radiology

1. HYPOTHALAMUS Presenter- Dr. N. Vinay Kumar DM Neurology resident

2. INTRODUCTION Latin word- hypo –below and thalamus- room or chamber. It is very small part of brain weighing about 4 gms . It controls all vegetative and endocrine process. Acts as organ of integration of homeostatis . 0.3 to-0.5 %of total brain. Sherrington regarded as head ganglion of ANS. Nauta described as nodal region in maintaining homeostasis.

3. DEVELOPMENT The 1st step is development of the  neural tube . Develops from  ectoderm   Trilaminar  embryo  invaginates to form the neural fold →  neural tube  (closed by 6 weeks) Neural tube  becomes the CNS.

4. Primary and secondary neural  vesicles The  neural tube  develops 3 “bulges” known as the primary  vesicles : Prosencephalon  ( forebrain ) → splits into 2 secondary  vesicles : Telencephalon  → cerebrum Diencephalon  goes on to form: Thalamus Hypothalamus Epithalamus (includes the  pineal gland ) Subthalamus Mesencephalon  ( midbrain , no secondary  vesicles ) →  midbrain Rhombencephalon  (hindbrain) → splits into 2 secondary  vesicles : Metencephalon : Pons Cerebellum Myelencephalon  →  medulla oblongata

5. Location Located in the center of the brain Just superior to the brainstem Forms part of the walls and floor of the 3rd ventricle Symmetrical; has right and left halves

6. Boundaries of the hypothalamus Boundary Structures Superior Thalamus Floor of the 3rd ventricle Anterior Anterior commissure Lamina terminalis Lateral Cerebral hemispheres Medial Medial 3rd ventricle Posterior Posterior commissure Aqueduct of Sylvius Inferior Optic chiasma Pituitary (hypophyseal) stalk and gland Brainstem

7. When observed from below , the hypothalamus is seen to be related to the following structures, from anterior to posterior: (1) the optic chiasma, (2) the tuber cinereum and the infundibulum, and (3) the mammillary bodies.

8. Rostrocaudal levels divided into 4 primary levels from anterior (rostral) to posterior (caudal). Preoptic:  found between the optic chiasma and anterior commissure : Lateral preoptic area Medial preoptic area Supraoptic:  anterior most level behind the preoptic area: Paraventricular nucleus Anterior nucleus Supraoptic nucleus Suprachiasmatic nucleus Tuberal :  between the supraoptic and mammillary levels: Lateral hypothalamus Dorsomedial nucleus Ventromedial nucleus Arcuate nucleus Mammillary:  posterior most (caudal) level: Posterior nucleus Mammillary bodies

9. Parasagittal zones Each ½ of the hypothalamus contain 3 primary zones or areas (from lateral to medial): Lateral hypothalamic area: diffuse fiber systems Medial hypothalamic area: contains the defined nuclei Periventricular gray zone: immediately adjacent to the 3rd ventricle

10. Nuclei are divided by an imaginary parasagittal plane into medial and lateral zones

11. Medial Zone anterior to posterior: (1) part of the preoptic nucleus; (2) anterior nucleus, which merges with the preoptic nucleus; (3) part of the suprachiasmatic nucleus; (4) paraventricular nucleus; (5) dorsomedial nucleus; (6) ventromedial nucleus; (7) infundibular (arcuate) nucleus; and (8) posterior nucleus.

12. Lateral Zone from anterior to posterior: (1) part of the preoptic nucleus, (2) part of the suprachiasmatic nucleus, (3) supraoptic nucleus, (4) lateral nucleus, (5) tuberomammillary nucleus, and (6) lateral tuberal nuclei. Some of the nuclei, such as the preoptic nucleus, the suprachiasmatic nucleus, and the mammillary nuclei, overlap both zones.

13. Neurovasculature The hypothalamus is a major coordinating center within the body. It receives information and can exert its effects via nerves, blood, and CSF. Afferent nerve connections of the hypothalamus Somatic nerves Visceral nerves  Visual/optic nerves  Olfactory nerves Cerebral cortex Hippocampus (via the fornix) Amygdala (via the stria terminalis) Thalamus Other nuclei within the hypothalamus

14. Efferent nerve connections of the hypothalamus The hypothalamus sends  efferent signals to: Descending fibers in the brain stem and  spinalcord  → affect peripheral auto nomic nervous system: Vagus nerve Sympathetic preganglionic neurons Mammillothalamic tract: mammillary body → thalamus Mammillotegmental tract: mammillary body → tegmentum of the midbrain (brainstem) Limbic system

15. Blood supply Arterial supply: The hypothalamus is supplied by the circle of Willis: Anterior cerebral artery → anteromedial branches Posterior communicating artery → posteromedial branches Posterior cerebral artery → thalamoperforating branches Venous drainage: Circle of intercavernous sinuses Hypothalamohypophyseal portal system

16. Connections with the pituitary gland   2 ways: via nerve fiber hypothalamohypophyseal tract  and via the circulation hypothalamohypophyseal portal system hypothalamohypophyseal tract Neurons in the paraventricular and supraoptic nuclei have direct projections that end in the posterior pituitary. Secretions include: Paraventricular nuclei: primarily produce oxytocin Supraoptic nuclei: primarily produce antidiuretic hormone

17. Hypothalamohypophyseal portal system Formed from branches off the internal carotid artery Arteries travel through the median eminence (the pituitary “stalk”) → capillaries Capillaries surround cells within the anterior lobe of the pituitary. Neurosecretory cells in the medial zone of the hypothalamus have projections to the median eminence and secrete hormones into the portal system: Releasing hormones: Corticotropin-releasing hormone (CRH) Thyrotropin-releasing hormone(TRH) Gonadotropin-releasing hormone(GnRH) Growth hormone–releasing hormone (GHRH) Release-inhibiting hormones: Somatostatin Dopamine

18. Thyrotropin-Releasing Hormone F irst of the hypothalamic releasing hormones to be identified; tripeptide structure It is elaborated by the anterior periventricular, paraventricular, arcuate, ventromedial, and dorsomedial neurons. It stimulates the release of TSH , dopamine and somatostatin to a slight degree. TRH may function as a central regulator of the autonomic nervous system. Growth Hormone-Releasing Hormone secreted by specialized tuberoinfundibular neurons. From posterior part of the arcuate and ventromedian hypothalamic nuclei and other neurons of the median eminence and pre mammillary area. Somatostatin, a 14-amino-acid peptide is secreted by neurons in the periventricular area and small cell part of the paraventricular nucleus.

19. Corticotropin-Releasing Hormone 14-amino-acid peptide, acts synergistically with vasopressin to release adrenocorticotropic hormone (ACTH) neurons lie in a portion of the paraventricular nucleus receive input from multiple regions of the nervous system, particularly via the noradrenergic pathways (from reticular neurons in the medulla and those of the locus ceruleus and tractus solitarius) and from many limbic structures. Gonadotropin-Releasing Hormone This 10-amino-acid peptide originates in the arcuate nucleus and is present in highest concentration near the median eminence It affects the release of (LH) and (FSH). GnRH is under the influence of other neuronal systems, which are modulated by catecholamines, serotonin, acetylcholine, and dopamine

20. Prolactin Inhibition (Dopamine) Dopamine is released by neurons in the region of the arcuate nucleus into the hypophyseal portal system of the median eminence. It inhibits the release of prolactin from lactotrophic cells of the anterior pituitary. Vasopressin and Oxytocin These are oligopeptides elaborated by cells of the supraoptic and paraventricular nuclei and are transported, through the stalk of the pituitary to its posterior lobe and are stored. Vasopressin , acting on the V2 receptors in kidney tubules, serves as the antidiuretic hormone (ADH) and, complemented by thirst mechanisms, maintains the osmolality of the blood. Oxytocin initiates uterine contraction and promotes lactation. Its release is stimulated by distention of the cervix, labor, breastfeeding, and estrogen.

21. Functions Hypothalamus plays a major role in: Hormone regulation and secretion Autonomic effects (e.g., HR, blood pressure, GI secretions and motility, etc.) Thermoregulation Food and water intake Sleep and circadian rhythms Memory Emotional behavior Sexual behaviour and reproduction

22. Preoptic level The preoptic area contains: Lateral preoptic area: a continuation of the lateral hypothalamic nuclei Medial preoptic area: Associated with sexual arousal and sexual dimorphism Produces/secretes GnRH → released into the hypothalamohypophyseal portal system Involved in thermoregulation Lesions in this region are associated with:  Loss of control of sexual behavior Amenorrhea Impotence

23. Supraoptic level The supraoptic level contains several important nuclei including (from superior to inferior): Paraventricular nucleus Medial division: synthesizes and secretes a number of hormones that regulate the pituitary gland CRH, TRH , GHRH , Somatostatin ,Dopamine (inhibits prolactin secretion) Intermediate division: synthesizes hormones that are released from the posterior pituitary gland Lateral division: has some direct projections into the  vagus nerve Anterior nucleus Involved in thermoregulation and sleep Lesions in this region may lead to hyperthermia. Supraoptic nucleus Has direct projections to the posterior  pitutary Suprachiasmatic nucleus Located just above the optic chiasma Gets direct input from the retina A “master biologic clock”

24. Tuberal level The tuberal level contains: Lateral hypothalamic nuclei: Involved in: Regulating appetite and satiety Digestive function Sleep Pain perception Blood pressure Lesions here may lead to:  Narcolepsy Motility or functional GI disorders Eating disorders (due to ↓↓ desire to eat) Dorsomedial nucleus Involved in: Physiologic circadian rhythms (e.g., eating and drinking, energy consumption) Ingestive behavior Cardiovascular response to stress Lesions here may lead to: overeating (hyperphagia), obesity

25. Ventromedial nucleus: Involved in: Appetite, satiety, and energy regulation Fear response via afferent input from the amygdala Lesions here may lead to: hyperphagia, obesity Arcuate nucleus:  A primary regulator of the anterior pituitary gland via the hypothalamohypophyseal portal system Secretes: GnRH Dopamine → regulates prolactin secretion Neuropeptide Y → regulates appetite and body weight Lesions here may lead to:  galactorrhea , hyperphagia

26. Mammillary level The mammillary level includes: Posterior nucleus:  Involved in thermoregulation (heating the body) Lesion here may lead to: hypothermia Mammillary bodies:  Involved in regulating emotions and recollective memory Lesion here may lead to: Memory deficits Pathogenesis of Wernicke encephalopathy

27. Autonomic functions Sherrington describes hypothalamus as head ganglion Anterior-parasympathetic Posterior – sympathetic. CVS regulation-posterior and lateral nuclei stimulation –tachycardia, hypertension and cutaneous vasoconstriction. Preoptic area is opposite. Pupil size- post and lat - dilatation. preoptic and supraoptic is opposite. Peristaltic and secretomotor functions of GIT- post and lateral decreases secretions and motility. ant and medial is opposite.

28. Sleep –wake cycle Ant hypothalamus- sleep facilitatory Post hypothalamus- waking center . Sleep-negative phenomenon-inhibition of waking center in post hypothalamus by ant hypothalamus-leads to sleep.

29. Food intake regulation Feeding center Lat hypothalamus nuclei. Stimulation increases food intake Its destruction -anorexia Satiety center Ventromedial nucleus Stimulation-stop food intake Destruction -hyperphagia

30. Food intake increased by Neuropeptide y Orexin A &B Melanin concentration hormone ghrelin Food in take decreased by CART CRH

31. Endocrinal function Controls pituitary hormone secretions. Control thyroid G Controls metabolism through adrenal gland Controls formation of milk by prolactin secretion Regulate water balance through ADH Regulation of uterine contractility and regulation of milk ejection through oxytocin

32. Neuro secretory cells Receive and process stimuli from all parts of CNS. Conduct action potentials along their axons and synthesize and release hormones into circulatory system. They produce peptide prohormones by mrna on ribosomes in their cell body and then convert prohormone to active hormones during process of axoplasmic transport along axon filaments. They store hormones in vesicular granules in terminals until depolarisation of plasma membrane causes exocytosis .

33. Circadian rhythm control Suprachiasmatic nucleus is main site to control. Biological clock receives inputs from eye- retino hypothalamic fibers . inputs that originate in the retina, synapse in the suprachiasmatic nucleus, pass through descending sympathetic tracts to the intermediolateral cell columns and superior cervical ganglia, and then ascend to innervate noradrenergic terminals on the pinealocytes . Darkness elicits a release of norepinephrine from these photoreceptors, ultimately stimulating the synthesis and release of melatonin. During daylight the retinal photoreceptor cells are hyperpolarized, norepinephrine release is inhibited, and melatonin secretion is suppress ed.

34. Temperature regulation Heat loss center Anterior hypothalamus ,preoptic area. Stimulation causes cutaneous vasodilatation and sweating Lesion-abolish response Heat gain center Posterior hypothalamus Stimulation causes vasoconstriction and shivering

35. Sexual behaviour and reproduction Pathway include- amygdala, stria terminalis , preoptic area , tuberal region. Connection maintains basal secretion of GnRh Stimulation of preoptic leads to cyclical surge – ovulation Lesion –prevents ovulation.

36. Emotional and instinctual behavior Limbic coretex . Concerned with affective nature of sensory impulses.

37. Hypothalamus and emotion The sham rage experiments established the hypothalamus as playing a prominent role in coordinating emotional behavior. Further studies by Stephen Ranson in the 1930s and by Walter Hess in the 1940s extended these findings. These investigators placed electrodes in the hypothalamus ( Ranson in anaesthetized animals, and Hess in unanaesthetized animals) and applied stimulation. Hess found that stimulating different parts of the hypothalamus produced characteristic reactions that appeared to correspond to specific emotional states. For example, stimulation of the lateral hypothalamus caused autonomic and somatic responses consistent with anger: increased blood pressure, raising of the body hair, pupillary constriction, etc. These studies lead to the view that the hypothalamus can facilitate the coordination of peripheral emotional responses.

38. Cannon-Bard theory of emotion and sham rage Bard, a student of Cannon’s, made serial transections, essentially disconnecting the cerebral cortex from outflow pathways in cats. When transection just included the forebrain (a), a range of behaviors constitutive of rage was observed when a cat was presented with innocuous stimuli. These behaviors included: Arching of the back Extension of claws Hissing Spitting Pupil dilation Increased blood pressure, heart rate and adrenal secretion

39. This rage was called “sham rage” because animals retained emotional responses, but the responses lacked aspects of emotional behavior that was normally observed during rage. Besides being elicited by innocuous stimuli, sham rage subsided rapidly upon stimulus removal and was undirected; animals even bit themselves. When Bard performed progressive transections (b and c), when the posterior hypothalamus was disconnected, no coordinated rage response was observed.

40. Reward and punishment center Reward centre – lateral and ventro medial nucleus. Punishment centre- medial hypothalamus. Controls body activities , drives,aversions and motivation.

41. Water balance regulation Through thirst centre Through osmoreceptors in supra optic nucleus.

42. Diseases affecting hypothalamus Pitutary adenoma Craniopharyngioma and rathke cleft cyst Suprasellar dysgerminoma Hypothalamic hamartoma Sarcoidosis Langerhans cell histiocytosis Vascular diseases

43. Effects of hypothalamic disease on pituitary function Can be hyper or hypo function of pituitary based on severity Hypothalamic hypogonadism Hypothalamic hyper prolactinoma. Tertiary hypothyroidism. Diabetes insipidus

44. Effects of hypothalamic disease on neurometabolic functions Hypothalamic obesity –destruction of mediobasal thalamus Hypothalamic anorexia –lesions in lateral hypothalamus Hyperglycemia –hypothalamus activation in stress Anorexia nervosa Bulemia nervosa Binge eating disorder

45. References Snell textbook of neuroanatomy. Saladin, K.S., Miller, L. (2004). Anatomy and Physiology, 3rd ed., pp. 530–531.  Castro, A., Merchut , M., Neafsey , E., Wurster R. (2002). Neuroscience: An Outline Approach. St. Louis: Mosby, pp. 369–375. Bear, M. (2021). Neuroanatomy, hypothalamus. StatPearls . Retrieved August 10, 2021, from  Kibble, J.D., Halsey, C.R. (2015). Neurophysiology. Chapter 2 of Medical Physiology: The Big Picture. New York: McGraw-Hill Education. , Barman, S.M., Brooks, H.L., Yuan, J.X. (2019). Hypothalamic regulation of hormonal functions. Chapter 17 of Ganong's Review of Medical Physiology, 26th ed. New York: McGraw-Hill Education. Retrieved August 10, 2021, from 

46. Thank you