Fifty Two and Fifty Three

Question 1

Generally, where is the hypothalamus located and what is its function?

Answer 1

Located beneath the thalamus at the ventral surface of the diencephalon forming the walls

of the third cerebroventricle, the hypothalamus is small in size (about 4 grams in the

adult) but is a major crossroad for emotional, autonomic and endocrine circuitry in the
brain. Afferents to the hypothalamus provide exteroceptive and enteroceptive information

that is then processed into neural and humoral signals responsible for the maintenance of

normal cardiovascular, renal, visceral and endocrine function, as well as for the

expression of appropriate and conditioned behavioral responses to our environment.

Question 2

What are the caudal, dorsal, ventral, and rostral borders of the hypothalamus?

Answer 2

Boundaries: Rostral – lamina terminalis

Caudal – posterior aspects of mamillary nuclei

Dorsal – hypothalamic sulcus (approximately a line connecting

the foramen of Monroe and the cerebral aqueduct)

Ventral – ventral surface of the diencephalon

Question 3

What are the 4 principal areas of the hypothalamus and what are the key landmarks/nuclei in each slice?

Answer 3

Preoptic – preoptic area, substantia inominata, septal nuclei, anterior commissure

Suprachiasmatic – optic chiasm, supraoptic nuclei, paraventricular nuclei, anterior hypothalamic nuclei, lateral
hypothalamic area, fornix

Tuberal – infundibulum with arcuate nucleus and median eminence, ventromedial and dorsomedial hypothalamic
nuclei, fornix, lateral hypothalamic area

Mamillary – mamillary nuclei, posterior hypothalamic area, fornix, mamillothalamic tract

Question 4

What is the arterial blood supply of the hypothalamus? What is the venous blood supply of the hypothalamus? Of the pituitary?

Answer 4

Arterial: Anteromedial arteries from anterior cerebral and anterior communicating

Posteromedial arteries from posterior cerebral and posterior communicating

Superior and inferior hypophysial arteries from internal carotids

Venous: Hypothalamus – basilar vein to great cerebral vein to straight sinus to transverse sinus to internal jugular

Pituitary – intercavernous sinus to transverse sinus to internal jugular

Question 5

What are 4 neural afferent fibers to the hypothalamus? What is their origin? What is their termination?

Answer 5

Medial forebrain bundle (#13)
Origin: septal and olfactory regions
Termination: most hypothalamic nuclei and midbrain reticular formation

Stria terminalis (#3)
Origin: amygdala
Termination: preoptic and septal nuclei, anterior hypothalamic area, ventromedial hypothalamic nuclei

Fornix (#2)
Origin: hippocampus and subiculum
Termination: mamillary nuclei, septal nuclei, anterior hypothalamic area, ventromedial hypothalamic area

Ventral amygdalofugal bundle (#16)
Origin: amygdala
Termination: lateral preoptic areas, septal nuclei, substantia innominata

Question 6

What are 4 efferent fibers from the hypothalamus? Origin/termination?

Answer 6

Mamillothalamic tract (#8)
Origin: mamillary nuclei
Termination: anterior thalamic nuclei

Periventricular fibers (Dorsal Longitudinal Fasciculus) (#9)
Origin: diffuse hypothalamus
Termination: brainstem parasympathetic nuclei, motor nuclei of the trigeminal, facial nuclei, nucleus ambiguus (IX, X, XI), and hypoglossal nuclei

medial forebrain bundle (see above)

Stria medullaris thalami (#4)
Origin: septal nuclei and preoptic area
Termination: habenula

Question 7

What are 2 examples of hypothalamic neural input/neural output?

Answer 7

Hypothalamic control of autonomic function and hypothalamic control of temperature regulation

Question 8

How are parasympathetics controlled by the hypothalamus? How is it manifest? Same questions for sympathetics.

Answer 8

Parasympathetics – stimulation of the anterior hypothalamus (preoptic and

suprachiasmatic regions) results in increased vagal and sacral parasympathetic activity (as manifested by reduced heart rate and increased visceral secretomotor function)

Sympathetics – stimulation of the lateral and posterior hypothalamus results in

increased sympathetic tone (as manifested by increased metabolic rate, increased heart

rate, increased vascular tone, increased rate and depth of respiration, and inhibition of

visceral secretomotor function….a.k.a. the stress reaction)

Question 9

What areas of the Hypothal are responsible for heat dissipation? How does this occur? What do lesions in this area result in?

Answer 9

Heat dissipation – thermal sensors in the preoptic and anterior hypothalamic areas

detect increases in the temperature of the blood supply and set in motion reflexes that

result in heat loss. Stimulation of this area causes sweating and cutaneous vasodilation.

[N.B. Here is one place where the distinction between parasympathetic and sympatheticfunction is an exception.

Lesions in the Preoptic and Anterior Hypothalamic Area disrupt the heat loss

mechanism resulting in the inability of the patient to “lose heat” (a.k.a. hyperpyrexia

associated with tumors in the anterior hypothalamus).

Question 10

What centers of the hypothal dectect drops in temp. of blood supply that lead to heat gain/conservation? How does this manifest? What do lesions there result in? Why?

Answer 10

Heat gain/conservation – thermal sensors in the posterior hypothalamus detect

drops in the temperature of the blood supply and set in motion reflexes that result in heat

conservation or formation (largely sympathetic in nature including a shift of blood flow away from the skin, increased metabolic rate and shivering). Selective stimulation in these areas can result in heat gain.

However, since the descending efferents that arose in
the “heat loss” centers of the anterior hypothalamus pass through this same region, lesions of the posterior hypothalamus result in the inability of the patient to either gain heat (in a cold environment) or lose heat (in a hot environment). These patient’s body temperature therefore fluctuates with the temperature of their environment (a.k.a. poikilothermia associated with tumors or infarcts in the posterior hypothalamus).

Question 11

What are some examples hypothalamic mixed neural input/mixed neural output?

Answer 11

Food Intake, Fluid Homeostasis

Question 12

What are two different theories of how the hypothalamus uses blood-borne signals to control food intake? Explain them. Which of the four regions does this occur in? What is the neural input of the hypothal that detects fullness? Where does it come from?

Answer 12

Two prevalent theories of the control of food intake (eating) center on the

hypothalamus as a receptor for blood-borne signals that activate feeding behaviors. Both

theories rely on the perception by hypothalamic neurons of the absolute levels of these

signals and give rise to the lipostatic and the glucostatic theories of food intake. In the

lipostatic theory, a lipophylic peptide, LEPTIN, produced in adipocytes crosses into the

brain and signals the fullness of the body’s fat stores. In the glucostatic theory, it is the

absolute levels of glucose in the circulation that signal adequacy of the fuel supply for the

brain and the other organs. Both theories place the receptive elements in the tuberal

region of the hypothalamus where the “feeding” and “satiety” centers are located. Neural input to the hypothalamus reporting relative “fullness” of the stomach is conveyed via neurons originating in the nucleus tractus solitarius and vagal nuclei.

Question 13

What centers are involved in the feeding center? What do bilateral lesions of this area result in? What centers are involved in the satiety center? What do bilateral lesions result in? What are these neurons actually responding to?

Answer 13

Feeding center – bilateral lesions in the lateral hypothalamic area of the tuberal hypothalamus result in hypophagia (decreased eating regardless of metabolic state and eventual wasting).

Satiety center – bilateral lesions of the ventromedial hypothalamic nuclei result in voracious appetite regardless of metabolic state (and in aggressive, often vicious behaviors).

Neurons responsive to both leptin and increased glucose concentrations (both of which inhibit feeding). Feeding center is activated by little glucose and inhibited by lots of leptin. Satiety center is activated by lots of glucose and leptin.

Question 14

What is the neural output of the feeding/satiety centers? What is the humoral output?

Answer 14

The neural output of these centers is primarily to motivational centers in cortex and motor centers regulating the behaviors of food gathering and eating. Neural outflow also innervates parasympathetic centers in brain stem regulating salivary secretion and visceral secretomotor activity. Humoral output is via regulation of anterior pituitary lobe hormones related to metabolism (e.g. adrenocorticotropin, growth hormone, and thyroid stimulating hormone).

Question 15

What happens when blood volume is increased? What is the pathway? What role does the hypothalamus play? What happens when blood volume is decreased? What is the pathway? What role does the hypothalamus play both neurally and humorally? What is AVP and what does it do? What tracts does the input to the hypothalamus run in?

Answer 15

Volume regulation – plasma volume is sensed primarily by baroreceptors located in the

aortic arch and carotid sinus. [Low pressure baroreceptors are also present in the heart

(atria) and the kidney.] Baroreceptor activity is determined by stretch (tension). When

volume status increases the sensory endings in the baroreceptors are depolarized and

afferent activity in the glossopharyngeal (IX) and vagus (X) nerves increases. That

activity exerts a negative effect in the brain stem (nucleus tractus solitarius) that is translated into a decrease in sympathetic outflow from the brain (and hence a slowing of the heart and vasorelaxation) and, via afferents to the hypothalamus (paraventricular and supraoptic nuclei), increased inhibition of VASOPRESSIN (AVP, a.k.a. ANTIDIURETIC HORMONE, ADH) release.

On the other hand when volume status decreases, the baroreceptor stretch is

relaxed (the receptors are “unloaded”) so less inhibitory activity arrives via IX and X and

sympathetic outflow increases (increased heart rate and vascular tone). Less inhibitory

input into hypothalamus results in AVP release. AVP stimulates the insertion of “pores

(aquaporins)” into the luminal membranes in the distal convoluted tubules and collecting

ducts of the kidney, resulting in a movement of free water down its concentration

gradient into the hypertonic interstitium of the renal medulla and therefore the “capture”

from the urine of water. Unloading of the baroreceptor (decreased plasma volume) also

signals via similar neuronal pathways the hypothalamic mechanisms regulating thirst,

resulting in increased fluid intake (to replace lost plasma volume). Thirst is a reflection of the neural output of the system, while AVP release represents the humoral mechanism.

Question 16

What are the two ways in which electrolyte balance can be mediated? What are the two places that sense plasma osmolality? What is their initial reaction to increases in plasma osmolality? What does this lead to? What about decreases in plasma osmolality?

Answer 16

Electrolyte balance –can be altered by increased thirst mechanisms and by changes in renal function dictated by adrenal steroids that are controlled at least in part by a
hypothalamic mechanism.

Increases in plasma osmolality are sensed by “osmoreceptors” in two circumventricular organs (where no blood brain barrier exists) adjacent to the hypothalamus, the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT). Increased plasma osmolality causes water to move out of
those cells and their shrinkage results in depolarization and the initiation of neural pathways activating thirst and stimulating AVP release. Decreases in plasma osmolality
result in the opposite effect, cell expansion, hyperpolarization and the absence of signals for thirst and AVP release.

Question 17

Where are sodium sensors located ? What do they monitor? what hapens when sodium levels fall? What hypothalamic center is this dependent on? What two circulating hormones inhibit thirst and salt appetite? Which circulating hormone stimulates thirst and salt appetite? What affects do these have in the hypothal and pituitary? What happens next?

Answer 17

There appear also to be “sodium sensors” in the SFO and OVLT that monitorabsolute levels of solutes, particularly sodium. When sodium levels fall, via similar mechanisms for those described for thirst (i.e. water intake), the generation of a salt appetite occurs. This depends upon the paraventricular nucleus of the hypothalamus and
its efferent outflow to behavioral and motivational centers in cortex and motor centers as well.

Humoral mechanisms regulating thirst (water intake) and salt appetite also exist and two circulating hormones (ATRIAL NATRIURETIC HORMONE and ADRENOMEDULLIN) have been demonstrated to inhibit thirst and salt appetite, while another (ANGIOTENSIN II) stimulates both behaviors. Those three circulating hormones also act in hypothalamus and pituitary gland to regulate the release of adrenocorticotropin (ACTH) which acts in the adrenal gland to stimulate primarily cortisol, but to some degree aldosterone, release. Cortisol is a physiologically relevant regulator of the renal handling of sodium via its action on the mineralocorticoid (aldosterone) receptor in the tissue.

decreased salt=Increased aldosterone, increased salt appetite

increased salt=decreased aldosterone, decreased salt appetite.

Question 18

Which hypothal centers are involved in reproductive changes? What is their input? What is their function? What do lesions result in in women? In men? other effects of lesions?

Answer 18

Changing levels of ovarian steroids influence the neuroendocrine function of the

hypothalamus and the behavioral mechanisms related to mating behavior. These actions of estrogen and progesterone determine the timing of the mid-cycle LH/FSH (luteinizing hormone and follicle stimulating hormone surges) and serve to organize, via the hypothalamus, the stereotypic motor behavior and motivational control of mating behavior in general.

Input to hypothalamus is via a direct action of the steroids on neurons in the preoptic/anterior hypothalamic areas (positive feedback) and the ventromedial hypothalamic nuclei (negative feedback). Lesions
in these areas block normal ovarian cyclicity in women and in men result in diminution of testosterone feedback stimulation of libido and sexual function (neural output).

Lesions also compromise the hypothalamic neurons that produce GONADOTROPIN
RELEASING HORMONE (GnRH) and therefore result in the absence of the neuroendocrine stimulation of LH and FSH releases (humoral output) and eventual gonadal hypofunction.

Question 19

What are two examples of hypothalamic neural input humoral output?

Answer 19

milk ejection reflex, stress induced anterior pituitary hormone secretion

Question 20

Explain the milk ejection reflex. The inputs, their pathways, the output. The manifestation.

Answer 20

Touch receptors in the nipple of the appropriately primed (hormonal) breast of the

lactating female send afferent information via the spinothalamic pathways and thalamus

into the hypothalamus where they innervate OXYTOCIN (OT) neurons in the

paraventricular and supraoptic nuclei. Touch of the nipples results in OT release and milk

ejection because of the presence of OT receptors on the smooth muscle cells surrounding

the lactiferous ducts of the breast. This reflex release of OT can also be stimulated by

sight and sound (exteroceptive information) or emotional components (cortical in origin).

Thus multiple neuronal inputs control the humoral mechanism (OT release into the circulation from nerve terminals in the posterior lobe of the pituitary gland).

Question 21

What are the two anterior lobe hormones released in response to physical/emotional stress? What is the input to the hypothalamus? Describe the pathway leading to the relsease of each of the hormones. Which hypothal. centers are used? What is the output? What is the effect? What do lesions of the median eminence result in? Why? What are the results?

Answer 21

Two anterior lobe hormones, prolactin (PRL) and ACTH, are released in response

to physical and/or emotional stress. Neural afferents to hypothalamic neurons come from exteroceptive sources (visual, auditory, olfactory, tactile) and input from cognitive
centers in cerebral cortex similarly can activate hypothalamic “stress centers.” In terms of ACTH release, neural afferents converge on the paraventricular nucleus where they stimulate the release of CORTICOTROPIN RELEASING HORMONE (CRH) that, upon access to the hypophysial portal vessels, travels the short distance from median eminence to the anterior lobe of the pituitary gland and stimulates ACTH release.

In terms of PRL release, a disinhibition occurs during stress. Under normal circumstance the release of
PRL from the anterior lobe is inhibited by the action of DOPAMINE arising in neurons in the arcuate (a.k.a. infundibular) nucleus of the hypothalamus. In stressful
circumstances, the release of dopamine into the median eminence is decreased, translating into less of an inhibitory signal entering the anterior lobe via the portal vessels and a rebound release of PRL.

Lesions of the median eminence result in the inability to mount an appropriate adrenal response (i.e. cortisol secretion) to stress and an inappropriately elevated level of PRL in plasma. The consequences of these elevated
PRL levels may include autoimmune disease and altered bone mineralization as well as abnormal reproductive function. Impaired cortisol release disrupts glucose homeostasis and can lead to dysregulated immune cell function.