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

8. • 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.

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

10. 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

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

13. • 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.

14. • 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.

15. 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

16. • 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

18. 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

19. 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

20. 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

23. Thyrotropin-Releasing Hormone
• First 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.

24. 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

25. 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.

26. 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

27. 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

28. 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”

29. 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

30. • 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

31. 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

33. 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.

34. 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.

35. 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

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

37. 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

39. 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.

42. 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 suppressed.

43. 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

45. 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.

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

47. 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.

48. 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

49. • 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.

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

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

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

53. 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

54. 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

57. References
1. Snell textbook of neuroanatomy.
2. Saladin, K.S., Miller, L. (2004). Anatomy and Physiology, 3rd ed., pp. 530–531.
3. Castro, A., Merchut, M., Neafsey, E., Wurster R. (2002). Neuroscience: An Outline Approach. St. Louis: Mosby, pp. 369–375.
4. Bear, M. (2021). Neuroanatomy, hypothalamus. StatPearls. Retrieved August 10, 2021, from
5. 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

58. Thank you