Hypothalamus Physiology Notes

Hypothalamus Introduction

Hypothalamus is a diencephalic structure. It is situated just below thalamus in the ventral part of the diencephalon. It is formed by groups of nuclei scattered in the walls and floor of third ventricle. It extends from optic chiasma to the mamillary body.

Nuclei Of Hypothalamus

The nuclei of the hypothalamus are divided into three groups:

1. Anterior or preoptic group
2. Middle or tuberal group
3. Posterior or mamillary group.

Read And Learn More: Medical Physiology Notes

The nuclei of each group are listed in Table and represented diagrammatically.

Connections Of Hypothalamus

Afferent Connections To Hypothalamus

1. Medial forebrain bundle: From rhinencephalon (limbic cortex) to preoptic nucleus, lateral nucleus and mamillary body
2. Fornix: From hippocampus to mamillary body
3. Striaterminalis: From amygdaloid to preoptic nucleus
4. Corticohypothalamic fibers: From prefrontal area (8) and precentral area (6) of cerebral cortex to the supraoptic and paraventricular nuclei of hypothalamus
5. Pallidohypothalamic fibers: From globus pallidus to diffused areas of hypothalamus
6. Thalamohypothalamic fibers: From dorsomedial and midline nuclei of the thalamus to diffused areas of hypothalamus
7. Fibers from reticular formation of the brainstem to diffused areas of the hypothalamus
8. Retinohypothalamic fibers: Fibers from retina to supraoptic, suprachiasmatic, and ventromedial nuclei of hypothalamus.

Efferent Connections From Hypothalamus

1. Mamillothalamic tract: From mamillary body to anterior thalamic nuclei
2. Mamillotegmental tract: From the mamillary body to the tegmental nuclei of the midbrain
3. Periventricular fibers: Fibers from posterior, supraoptic, and tuberal nuclei of the hypothalamus pass through periventricular gray matter and reach the following:
   1. Reticular formation in the brainstem and spinal cord
   2. Dorsomedial nucleus of thalamus
   3. Frontal lobe of the cerebral cortex
4. Hypothalamo-hypophyseal tract: From supraoptic and paraventricular nuclei of the hypothalamus to posterior pituitary.

Functions Of Hypothalamus

Hypothalamus is the impbrtant part of the brain concerned with homeostasis of the body. It regulates many vital functions of the body like endocrine functions, visceral functions, metabolic activities, hunger, thirst, sleep, wakefulness, emotion, sexual functions, etc.

1. Secretion Of Posterior Pituitary Hormones:

• Hypothalamus is the site of secretion for the posterior pituitary hormones. Antidiuretic hormone (ADH) and oxytocin are secreted by supraoptic and paraventricular nuclei.
• These two hormones are transported by means of axonic or axoplasmic flow through the fibers of hypothalami-hypophyseal tracts to the posterior pituitary.

2. Control Of Anterior Pituitary: Hypothalamus controls the secretions of the anterior pituitary gland by secreting releasing hormones and inhibitory hormones. It secretes seven hormones.

1. Growth hormone-releasing hormone (GHRH)
2. Growth hormone-releasing polypeptide (GHRP)
3. Growth hormone inhibitory hormone (GHIH) or somatostatin
4. Thyrotropic releasing hormone (TRH)
5. Corticotropin-releasing hormone (CRH)
6. Gonadotropin-releasing hormone (GnRH)
7. Prolactin inhibitory hormone (PIH).

• These hormones are secreted by discrete areas of hypothalamus and transported to the anterior pituitary by the hypothalamo-hypophyseal portal blood vessels.

3. Control Of Adrenal Cortex: Anterior pituitary regulates the adrenal cortex by secreting adrenocorticotropic hormone (ACTH). ACTH secretion is in turn regulated by corticotropic releasing hormone (CRH) which is secreted by the paraventricular nucleus of the hypothalamus.

4. Control Of Adrenal Medulla: Demccmulsl and posterior hypothamic nuclei are excited by emotional stimuli. These hypothalamic nuclei, in turn, send impulses to the adrenal medulla through sympathetic fibers and cause release of catecholamines, which are essential to cope up with emotional stress.

5. Regulation Of Autonomic Nervous System: Hypothalamus controls the autonomic nervous system (ANS). The sympathetic division of ANS is regulated by posterior and lateral nuclei of hypothalamus. The parasympathetic division of ANS is controlled by anterior group of nuclei. The influences of the cerebral cortex on ANS are executed through hypothalamus

6. Regulation Of Heart Rate: Hypothalamus regulates heart rate through vasomotor center in the medulla oblongata. Stimulation of posterior and lateral nuclei of the hypothalamus increases the heart rate. Stimulation of preoptic nucleus in the anterior group decreases the heart rate.

7. Regulation Of Blood Pressure: Hypothalamus regulates the blood pressure by acting on the vasomotor center. Stimulation of posterior and lateral hypothalamic nuclei increases arterial blood pressure and stimulation of preoptic area decreases the blood pressure.

8. Regulation Of Body Temperature: The body temperature is regulated by the hypothalamus which sets the normal range of body temperature. The set point under normal physiological conditions is 37°C.

• Hypothalamus has two centers that regulate the body temperature:
  1. Heat loss center that is present in preoptic nucleus of the anterior hypothalamus
  2. Heat gain center that is situated in posterior hypothalamic nucleus.
• Regulation of body temperature is explained.

9. Regulation Of Hunger And Food Intake: Food intake is regulated by two centers present in hypothalamus:

1. Feeding Center
   • Feeding center is in the lateral hypothalamic nucleus. In experimental conditions, the stimulation of this center in animals leads to uncontrolled hunger and increased food intake (hyperphagia) resulting in obesity.
   • The destruction of the feeding center leads to loss of appetite (anorexia) and the animal refuses to take food. Normally feeding center is always active. That means it has the tendency to induce food intake always.
2. Satiety Center:
   • Satiety center is in the ventromedial nucleus of the hypothalamus. Stimulation of this nucleus in animals causes total loss of appetite and cessation of food intake.
   • Destruction of satiety center leads to hyperphagia and the animal becomes obese. This type of obesity is called hypothalamic obesity.
   • Satiety center plays important role in regulation of food intake by temporary inhibition of feeding center after food intake.

• Mechanism of Regulation of Food Intake:
  • Under normal physiological conditions appetite and food intake are well balanced and continues in a cyclic manner.
  • Feeding center and satiety center of hypothalamus are responsible for regulation of appetite and food intake. These hypothalamic centers depend upon several mechanisms to execute this function. Such mechanisms are:
    1. Glucostatic Mechanism
       • The cells of the satiety center function as glucostats or glucose receptors. The glucostats are stimulated by increased blood glucose level. This is what happens during food intake. While taking food, the blood glucose level increases.
       • Slowly it activates the satiety center and at one stage it develops the feeling of ‘fullness’. The satiety center in turn, inhibits the feeding center resulting in stoppage of food intake.
       • After few hours of food intake, the blood glucose level decreases and satiety center becomes inactive. So, the feeding center is no longer inhibited.
       • Now it becomes active and increases the appetite and induces food intake. After taking food, once again blood glucose level increases and the cycle is repeated.
       • However, glucostats do not give response to very high level of glucose in the blood (hyperglycemia). So, in conditions like diabetes, hyperglycemia fails to stimulate the satiety center.
       • The satiety center does not inhibit the feeding center, so the frequency of food intake increases (polyphagia).
    2. Lipostatic Mechanism
       • Leptin acts on hypothalamus and inhibits the feeding center resulting in loss of appetite and stoppage of food intake. Leptin is a peptide secreted by adipocytes (cells of adipose tissue). It plays an important role in controlling food intake and adipose tissue volume.
       • When the volume of adipose tissues increases, adipocytes secrete and release a large quantity of leptin into the blood While circulating through brain, leptin crosses the blood-brain barrier and enters hypothalamus.
       • It is suggested that the cells present in the blood-brain barrier contain many receptor-like proteins which are responsible for the transport of leptin across the barrier.
         • Mode of action of leptin: Leptin acts through some specific neuropeptides in the hypothalamus such as:
           1. Neuropeptide Y: It is secreted in small intestine, medulla and hypothalamus. Normally, this peptide stimulates food intake. But, leptin inhibits neuropeptide Y leading to stoppage of food intake
           2. Pro-opiomelanocortin (POMC): It is secreted from the anterior pituitary. It is also secreted from the hypothalamus, lungs, Gl tract, and placenta. Normally, it inhibits food intake. Leptin stimulates secretion of POMC.
         • Leptin receptor: Many leptin receptors are identified. However, leptin acts via ‘LepRb’ which is the only active receptor present in many nuclei of hypothalamus.
    3. Peptide Mechanism:
       • Some peptides regulate food intake either by stimulating or inhibiting the feeding center directly or indirectly. The important one among the peptides is ghrelin.
       • Ghrelin is secreted in stomach during fasting. It directly stimulates the feeding center and increases the appetite and food intake. Besides ghrelin, several other peptides are involved in the regulation of food intake.
       • The peptides which increase the food intake are:
         1. Ghrelin
         2. Neuropeptide Y.
       • Peptides that decrease food intake are:
         1. Leptin
         2. Peptide YY.
    4. Hormonal Mechanism: Some of the endocrine hormones and Gl hormones inhibit food intake by acting through hypothalamus. Such hormones are:
       1. Somatostatin
       2. Oxytocin
       3. Glucagon
       4. Pancreatic polypeptide
       5. Cholecystokinin.
    5. Thermostatic Mechanism: Food intake is inversely proportional to body temperature. So in fever, the food intake is decreased. The exact mechanism of this fact is not known. It is suggested that the preoptic thermoreceptors may act via feeding center. The cytokines are also suggested to play a role in decreasing the appetite during fever.

10. Regulation Of Water Balance: Hypothalamus regulates water content of the body by two mechanisms:

1. Thirst Mechanism
   • Thirst center is in the lateral nucleus of the hypothalamus. There are some osmoreceptors in the areas adjacent to the thirst center. When the ECF volume decreases the osmolality of ECF is increased.
   • If the osmolarity increases by 1-2%, the osmoreceptors are stimulated. Osmoreceptors in turn, activate the thirst center, and the thirst sensation is initiated. Now, the person feels thirsty and drinks water. Water intake increases ECF volume and decreases osmolality.
2. ADH Mechanism
   • Simultaneously, when the volume of ECF decreases with increased osmolality, the supraoptic nucleus is stimulated and ADH is released. ADH causes the retention of water by facultative reabsorption in the renal tubules. It increases the ECF volume and brings the osmolality back its normal level.
   • On the contrary, when ECF is increased, the supraoptic nucleus is not and ADH is not secreted. In the absence of ADH, more amount of water is excreted through urine and the volume of ECF is brought back to normal.

11. Regulation Of Sleep And Wakefulness: Mammary body in the posterior hypothalamus is considered as the wakefulness center. Stimulation of the mamillary body causes wakefulness and its lesion leads to sleep. Stimulation of anterior hypothalamus also leads to sleep.

12. Role In Behavior And Emotional Changes

• The behavior of animals and human beings is mostly affected by two responding systems in hypothalamus and other structures of the limbic system. These two systems act opposite to one another.
• The responding systems are concerned with the affective nature of sensations, i.e. whether the sensations are pleasant or painful. These two qualities are called Reward (satisfaction) and punishment (aversion or avoidance).
• Hypothalamus has two centers for behavior and emotional changes are:
  1. Reward Center: It is situated in medial forebrain bundle and ventromedial nucleus of the hypothalamus. Electrical stimulation of these areas in animals pleases or satisfies the animals.
  2. Punishment Center: It is situated in the posterior and lateral nuclei of the hypothalamus. Electrical stimulation of these nuclei in animals leads to pain, fear, defense, escape reactions, and other elements of punishment.
• Role of Reward and Punishment Centers
  • The importance of the reward and punishment centers lies in the behavioral pattern of the individuals. Almost all the activities of day-to-day life depend upon reward and punishment.
  • While doing something, if the person is rewarded or feels satisfied, he or she continues to do so. If the person feels punished or unpleasant, he or she stops doing so. Thus, these two centers play an important role in the development of the behavioral pattern of a person.
• Rage: Rage refers to violent and aggressive emotional expression with extreme anger, it can be developed in animals by stimulating the punishment centers in the posterior and lateral hypothalamus. The reactions of rage are expressed by developing a defense posture which includes:
  1. Extension of limbs
  2. Lifting of tail
  3. Hissing and spitting
  4. Piloerection
  5. Wide opening of eyeballs
  6. Dilatation of pupil
  7. Severe savage attack even by mild provocation.
• Sham Rage
  • Sham rage means false rage. It is an extreme emotional condition that resembles rage and occurs in some pathological conditions in humans.
  • In physiological conditions, the animals and human beings maintain a balance between rage and its opposite state. This balanced condition is called the calm emotional state.
  • A major irritation may make a person to loose their temper. However, minor irritations are usually ignored or overcome. It is because of the inhibitory influence of the cerebral cortex on the hypothalamus.
  • But the calm emotional state is altered during brain lesions. In some cases, even a mild stimulus evokes sham rage. It can occur in decorticated animals also.
  • Sham rage is due to the release of the hypothalamus from the inhibitory influence of cortical control.

13. Regulation Of Sexual Function

• In animals, the hypothalamus plays an important role in maintaining sexual functions, especially in females. A decorticate female animal will have a regular estrus cycle provided the hypothalamus is intact.
• In human being also, hypothalamus regulates the sexual functions by secreting gonadotropin-releasing hormones. Arcuate and posterior hypothalamic nuclei are involved in the regulation of sexual functions.

14. Role In Response To Smell: The posterior hypothalamus along with other structures like the hippocampus and brainstem nuclei is responsible for the autonomic responses of body to olfactory stimuli. The responses include feeding activities and emotional responses like fear, excitement, and pleasure.

15. Role In Circadian Rhythm

• Circadian rhythm is the regular recurrence of physiological processes or activities which occur in cycles of 24 hours, t is also called diurnal rhythm. The term is circadian is a Latin word meaning ‘around the day’.
• The circadian rhythm occurs in response to recurring daylight and darkness. The cyclic changes taking place in various physiological processes are set by means of a hypothetical internal clock that is often called a biological clock.
• The suprachiasmatic nucleus of the hypothalamus plays an important role in setting the biological clock by its connection with retina via retinohypothalamic fibers.
• Through the efferent fibers, it sends circadian signals to different parts and maintains the circadian rhythm of sleep, hormonal secretion, thirst, hunger, appetite, etc.
• Whenever the body is exposed to a new pattern of daylight/ darkness rhythm, the biological clock is reset provided the new pattern is regular. Accordingly, the circadian rhythm also changes.

Applied Physiology Disorders Of Hypothalamus

• The lesion of the hypothalamus occurs due to tumors, encephalitis, and ischemia. The following features develop in the hypothalamic lesion:

1. Disturbances in carbohydrate and fat metabolisms when lateral, arcuate, and ventromedial nuclei are involved in lesion.
2. Disturbance in sleep due to lesions in the mamillary body and anterior hypothalamus.
3. Disturbance in sympathetic or parasympathetic function occurs due to lesions in posterior, lateral, and anterior nuclei.
4. Emotional manifestations leading to sham rage due to lesions in the ventromedial and posterolateral parts.
5. Disturbance in sexual functions due to the lesion in the mid-hypothalamus.
   • One or more of the above features can become prominent resulting in some clinical manifestations such as:
     1. Diabetes insipidus
     2. Dystrophia adiposogenitalis
     3. Kallmann’s syndrome
     4. Laurence-Moon-Biedl syndrome
     5. Narcolepsy
     6. Cataplexy.

1. Diabetes Insipidus: Diabetes insipidus is a condition characterized by the excretion of large quantities of water through urine.
2. Dystrophia Adiposogenitalis: It is characterized by obesity and sexual infantilism, associated with dwarfism (if the condition occurs during the growing period). It is also called Frohlich’s syndrome.
3. Kallmann’S Syndrome: Kallmann’s syndrome is a genetic disorder characterized by hypogonadism associated with anosmia (loss of olfactory sensation) or hyposmia (decreased olfactory sensation). It is also called hypogonadotropic hypogonadism since it occurs due to a deficiency of gonadotropic-releasing hormones secreted by the hypothalamus.
4. Laurence-Moon-Biedl Syndrome: This disorder of the hypothalamus is characterized by a moon face (facial contours become round by hiding the bony structures), obesity, polydactylism (having one or more extra fingers or toes), mental retardation, and hypogenitalism.
5. Narcolepsy: Narcolepsy is a hypothalamic disorder with abnormal sleep patterns. There is a sudden attack of uncontrollable desire for sleep and, the person suddenly falls asleep. It occurs in the daytime. The sleep may resemble normal sleep. The duration of sleep is very short. It may be from few seconds to 20 minutes. At night, sleep may be normal but is often disturbed or there may be insomnia (loss of sleep).
6. Cataplexy: It is the sudden uncontrolled outbursts of emotion associated with narcolepsy. Due to emotional outburst like anger, fear, or excitement, the person becomes completely exhausted with muscular weakness. The attack is brief and last for few seconds to a few minutes. The consciousness is not lost.