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

Nuclei of hypothalamus are divided into three groups:

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

Connections of hypothalamus are represented by afferent and efferent connections.

Afferent Connections

Hypothalamus receives connections from:

Efferent Connections

Hypothalamus sends connections to:

• Anterior nucleus of thalamus
• Midbrain
• Reticular formation
• Dorsomedial nucleus of thalamus
• Frontal cortex
• Posterior pituitary

Control of Anterior Pituitary

Hypothalamus controls the secretions of anterior pituitary gland by secreting releasing hormones and inhibitory hormones.

Hypothalamic Hormones Controlling Anterior Pituitary

Hypothalamus secretes seven hormones to control anterior pituitary:

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

All the above hormones are transported from hypothalamus to anterior pituitary by hypothalamic-hypophyseal portal blood vessels.

Secretion of Posterior Pituitary Hormones

Posterior pituitary hormones namely antidiuretic hormone (ADH) and oxytocin are secreted by supraoptic and paraventricular nuclei of hypothalamus.

Both the hormones are transported by means of axonic or axoplasmic flow through the fibers of hypothalamo-hypophyseal tract to posterior pituitary.

Control of Adrenal Cortex

Hypothalamus controls adrenal cortex through anterior pituitary.

Anterior pituitary regulates the adrenal cortex by secreting adrenocorticotropic hormone (ACTH).

ACTH secretion is in turn regulated by corticotropin-releasing hormone (CRH), which is secreted by paraventricular nucleus of hypothalamus.

Control of Adrenal Medulla

Dorsomedial and posterior hypothalamic nuclei are excited by emotional stimuli.

Both the hypothalamic nuclei, in turn, send impulses to adrenal medulla through sympathetic fibers and cause release of catecholamines.

Catecholamines help to cope up with emotional stress.

Hypothalamus regulates the activities of autonomic nervous system (ANS).

• Sympathetic division of ANS is regulated by posterior and lateral nuclei of hypothalamus.
• Parasympathetic division of ANS is regulated by anterior group of nuclei.
• Cerebral cortex influences ANS through hypothalamus.

Hypothalamus regulates heart rate through vasomotor center in the medulla oblongata.

• Stimulation of posterior and lateral nuclei of hypothalamus increases the heart rate.
• Stimulation of preoptic and anterior nuclei decreases the heart rate.

Hypothalamus regulates the blood pressure by acting on vasomotor center.

• Stimulation of posterior and lateral nuclei increases arterial blood pressure.
• Stimulation of preoptic area decreases the blood pressure.

Body temperature is regulated by hypothalamus which sets the normal range of body temperature.

The set point under normal physiological conditions is 37°C.

Centers for Regulation of Body Temperature

1. Heat loss center → situated in preoptic nucleus of anterior hypothalamus.
2. Heat gain center → situated in posterior hypothalamic nucleus.

Hypothalamus has two centers to regulate food intake:

1. Feeding center.
2. Satiety center.

Feeding Center

Feeding center is in lateral hypothalamic nucleus.

Normally, feeding center is always active. That means it has the tendency to induce food intake always.

In experimental conditions, stimulation of this center in animals leads to uncontrolled hunger and increased food intake (hyperphagia) resulting in obesity.

Destruction of feeding center leads to loss of appetite (anorexia) and the animal refuses to take food.

Satiety Center

Satiety center is in the ventromedial nucleus of hypothalamus.

Satiety center regulates food intake by temporary inhibition of feeding center after food intake.

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.

Mechanism of Regulation of Food Intake

Under normal physiological conditions, appetite and food intake are well balanced and continue in a cyclic manner.

Feeding center and satiety center of hypothalamus are responsible for regulation of appetite and food intake.

Hypothalamic centers are regulated by the following mechanisms:

1. Glucostatic mechanism.
2. Lipostatic mechanism.
3. Peptide mechanism.
4. Hormonal mechanism.
5. Thermostatic mechanism.

Glucostatic Mechanism

Cells of the satiety center function as glucostats or glucose receptors.

Glucostats are stimulated by increased blood glucose level during food intake.

This develops feeling of fullness.

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.

Feeding center is no longer inhibited.

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.

Lipostatic Mechanism

Leptin is a peptide secreted by adipocytes (cells of adipose tissue).

Leptin plays an important role in controlling food intake and adipose tissue volume.

When volume of adipose tissues increases, adipocytes secrete and release a large quantity of leptin into the blood.

While circulating through brain, leptin acts on hypothalamus and inhibits the feeding center resulting in loss of appetite and stoppage of food intake.

Peptide Mechanism

Some peptides regulate food intake either by stimulating or inhibiting the feeding center directly or indirectly.

Peptides Increasing Food Intake

1. Ghrelin.
2. Neuropeptide Y.

Hormonal Mechanism

Some endocrine hormones and GI hormones inhibit the food intake by acting through hypothalamus.

Hormones Inhibiting Food Intake

1. Glucagon.
2. Somatostatin.
3. Pancreatic polypeptide.
4. Cholecystokinin.
5. Oxytocin.

Thermostatic Mechanism

Food intake is inversely proportional to body temperature.

So, in fever food intake is decreased due to the influence of preoptic thermoreceptors on feeding center.

Hypothalamus regulates water content of body by two mechanisms:

1. Thirst mechanism.
2. ADH mechanism.

Thirst Mechanism

Thirst center is in lateral nucleus of hypothalamus.

Some osmoreceptors are present in areas adjacent to thirst center.

When ECF volume decreases, the osmolality of ECF is increased.

When osmolarity increases by 1 to 2%, the osmoreceptors are stimulated.

Osmoreceptors in turn activate the thirst center.

Thirst center induces thirst leading to water intake.

Water intake increases ECF volume and decreases the osmolality.

ADH Mechanism

Simultaneously, when volume of ECF decreases with increased osmolality, supraoptic nucleus is stimulated and ADH is released.

ADH causes retention of water by facilitating reabsorption in the renal tubules.

It increases ECF volume and brings osmolality back to normal level.

On the contrary, when ECF volume is increased, supraoptic nucleus is not stimulated 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.

Wakefulness Center

Mammillary body in posterior hypothalamus acts as the wakefulness center.

Stimulation of mammillary body causes wakefulness and its lesion leads to sleep.

Stimulation of anterior hypothalamus leads to sleep.

Behavior of animals and human beings is mostly affected by two responding systems in hypothalamus and other structures of limbic system.

These two systems act opposite to one another.

Responding systems are concerned with affective nature of sensations, i.e., whether the sensations are pleasant or painful.

These two qualities are called the reward (satisfaction) and punishment (aversion or avoidance).

Centers for Behavior and Emotional Changes

1. Reward center.
2. Punishment center.

Reward Center

Reward center is situated in medial forebrain bundle and ventromedial nucleus of hypothalamus.

Electrical stimulation of these two areas in animals satisfies the animals.

Punishment Center

Punishment center is situated in posterior and lateral nuclei of hypothalamus.

Electrical stimulation of these two nuclei in animals leads to pain, fear, defense, escape reactions and other elements of punishment.

Role of Reward and Punishment Centers

Importance of reward and punishment centers lies in the behavioral pattern of individuals.

Almost all the activities of day-to-day life depend upon reward and punishment.

While doing something, if the person is rewarded, he or she continues to do so.

If the person feels punished or unpleasant, he or she stops doing so.

Thus, reward and punishment centers play an important role in the development of the behavioral pattern of a person.

Rage

Rage is a violent and aggressive emotional expression with extreme anger.

It is common in animals when punishment centers in hypothalamus are stimulated.

Reactions of rage are expressed by developing a defense posture which includes:

1. Extension of limbs with lifting of tail.
2. Hissing and spitting.
3. Piloerection.
4. Wide opening of eyeballs with pupillary dilatation.
5. 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.

Sham rage is due to release of hypothalamus from the inhibitory influence of cortical control.

Hypothalamus regulates sexual functions by secreting gonadotropin-releasing hormone.

Arcuate and posterior hypothalamic nuclei are involved in the regulation of sexual functions.

Posterior hypothalamus along with other structures such as hippocampus and brainstem nuclei is responsible for the autonomic responses of body to olfactory stimuli.

Responses include feeding activities and emotional responses like fear, excitement and pleasure.

Circadian rhythm develops in response to recurring daylight and darkness.

Cyclic changes taking place in various physiological processes are set by means of a hypothetical internal clock that is often called biological clock.

Role of Suprachiasmatic Nucleus

Suprachiasmatic nucleus of hypothalamus sets 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 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.

Lesion in hypothalamus occurs due to tumors, encephalitis and ischemia.

Features Developed During Hypothalamic Lesion

1. Disturbances in carbohydrate and fat metabolisms occur when lateral, arcuate and ventromedial nuclei are involved in lesion.
2. Disturbance in sleep occurs due to lesion in mammillary body and anterior hypothalamus.
3. Disturbance in sympathetic or parasympathetic function occurs due to lesion in posterior, lateral and anterior nuclei.
4. Emotional manifestations occur leading to sham rage due to lesion in ventromedial and posterolateral parts.
5. Disturbance in sexual functions occurs due to lesion in mid hypothalamus.

One or more of the above features can become prominent resulting in following clinical manifestations:

Diabetes Insipidus

Diabetes insipidus is the condition characterized by excretion of large quantity of water through urine.

Dystrophia Adiposogenitalis

Dystrophia adiposogenitalis is characterized by obesity and sexual infantilism, associated with dwarfism (the condition occurs during growing period).

It is also called Frohlich’s syndrome.

Kallmann Syndrome

Kallmann 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 deficiency of gonadotropin-releasing hormone secreted by hypothalamus.

Laurence-Moon-Biedl Syndrome

This disorder of hypothalamus is characterized by 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.

Narcolepsy

Narcolepsy is a hypothalamic disorder with abnormal sleep pattern.

There is sudden attack of uncontrollable desire for sleep and the person suddenly falls asleep.

It occurs in the daytime.

Sleep may resemble the normal sleep.

Duration of sleep is very short.

It may be from few seconds to 20 minutes.

In night, sleep may be normal, but is often disturbed or there may be insomnia (loss of sleep).

Cataplexy

Cataplexy is the sudden uncontrolled outbursts of emotion associated with narcolepsy.

Due to emotional outbursts like anger, fear or excitement, the person becomes completely exhausted with muscular weakness.

The attack is brief and lasts for few seconds to a few minutes.

Consciousness is not lost.