Download Hypothalamus

Hypothalamus
Marco Celio
Mai 2010
Historical
Plates from the seventh
book of the first edition
(1543) of the Fabrica by
Andreas Vesalius, showing
what is believed to be the
oldest anatomical images
in Western literature of the
hypothalamic-pituitary
unit.1) Enlarged view of the
pituitary gland (A),
hypothalamic infundibulum
(B) and ducts comprising
the foramen lacerum and
superior orbital fissure (C,
D, E, F) believed to drain
the brain mucus or phlegm
(in Latin pituita) from the
pituitary gland to the
nasopharynx;
2) anatomical relationships
between the infundibulum
(D), the dural diaphragma
sellae (F), the internal
carotid arteries (C, D) and
the oculomotor nerve.
Drawings by Leonardo da Vinci (1508-1509) taken from the Codici di Anatomia of the Windsor’s Collection
(A) Inferior surface of the brain, showing the rete mirabilis (arrow) that surrounds the pituitary gland;
(B) three-dimensional representation of the cerebral ventricles. The third ventricle (3v) was believed to be the
site of afference and elaboration of the "sensus communis” (Latin for peripheral physical sensations)
Historical
• John Newport Langley (1852-1925)
– Introduced
• the term autonomic nervous system
• the concept of antagonism between sympathicus
and vagus
• and discovered preganglionic and postganglionic
cells
Historical
• Walter Bradford Cannon (1871-1945)
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Circuits in the central nervous system are responsible for the integrative action of the
autonomic nervous system
Cannon was influenced by the Harvard philosopher William James according to
whom the emotional state of an organism is associated with afferent feedbacks from
the body, notably from vascular and visceral structures
Cannon proposed that the different emotional states are represented in the brain
rather being peripheral in origin and are expressed by changes of activity in the
sympathetic and parysympathetic nervous system
Cannon view of the autonomic nervous system was that of a system designed to
preserve life during grave physical crisis requiring extreme efforts (« fight or flight »)
Writes the book: « The wisdom of the body »
Introduces the concept of « homeostasis »
Parasympathetic system conserve body energy
Claude Bernard: « le milieu intérieur »
Historical
• Walter Rudolf Hess (1881-1973)
• Observed the behavior elicited in conscious
cats by local electrical stimulation of the hypothalamus
• Transferred the idea of a dichotomy of the functional organization of
the autonomic nervous system to the hypothalamus
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Rostral part: integrate somatic, autonomic and endocrine reactions
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Promote revovery and conservation of energy, digestion, excretion and evacuation of waste
as well as reproductive function – parasympathetic nervous system -- trophotrophc reaction
Caudal part: general activation of the sympathetic nervous system
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Mobilization of body energy and enhancement of performance capacity (ergotropic reaction)
Whereas earlier studies found that electrical stimulation or lesions in the hypothalamus
profoundly affect autonomic function, more recent investigation have demonstrated that
many of these effects are due to the involvement of descending and ascending pathways
of the cerebral cortex or the basal forebrain passing through the hypothalamus.
Axonal tracing
Hypothalamus
• 1% of brain volume (4 gr)
• connected to all part of the nervous
system (2’000 projections)
• 50 to 100 different group of neurons
(nuclei)
• Masterplan similar in all mammalian
Characterized by the projection of their axons, their synaptic inputs and their histochemistry
Immunohistohemistry
(in-situ hybridisation)
The hypothalamus integrates autonomic
and endocrine functions with behavior
The hypothalamus serves this integrative
function be regulating six basic principal
needs:
Drinking and salt appetite,
maintenance of blood osmolality and
vasomotor tone
– blood pressure and electrolyte concentration
Control of metabolic thermogenesis and
behaviors such as seeking a warmer or
– body temperature
cooler environment
By feeding, digestion and
– energy metabolism
metabolic rate
Through hormonal control
– reproduction
of mating, pregnancy and lactation
flow to muscle
– emergency responses (stress) Blood
and other tissues and secretion of
adrenal stress hormones
– emotional response
The hypothalamus regulates these basic life
processes by recourse to 3 main mechanisms
• Receiving sensory information from virtually the entire
body. Direct inputs from the retina, olfactory system and
visceral sensory system. Inputs from the
circumventricular organs. Internal sensory neurons
responsive to changes in temperature, osmolality,
glucose and Na+.
• Comparing sensory information with biological set
points (temperature, osmolality, Na+, etc.)
• Adjusting deviations from a set point by an array of
autonomic, endocrine and behavioral responses.
If the body is too warm the hypothalamus intervene by:
• shifting blood flow from deep to cutaneous vascular beds
• increasing sweating and heat loss through the skin
• increasing vasopressin secretion to conserve water for sweating
• activating coordinated behaviors (seeking a cooler environment)
Homeostasis
/
• Stability of systems
that maintain life
– pH
– concentration of
different ions in the
extracellular fluid (Na+,
Ca2+)
– osmolality of
extracellular fluid
– glucose levels
– arterial oxygen tension
Constantly present
Allostasis
• Adaptation to
changing external and
internal environment
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arterial blood pressure
heart rate
body core temperature
concentration of
circulating hormones
– sleep-wake cycle
– energy metabolism
Temporary process, e.g. under stress
Circumventricular organs
Area postrema
Blood-brain barrier absent
Blood – brain barrier
Blood capillary with fenestrated endothelium and a wide perivascular space. They are typical in
circumventricular organs. L - lumen, blue arrow - endothelial pore, red arrow - basal lamina, P perivascular space, F - fibrocyte. Inset: blood capillary with the wide perivascular space. Scale = 200
nm. (Rat, area postrema.)
Inputs
Hypothalamic afferences
Output
Pituitary
Median eminence
ependymal zone (E),
internal zone (ZI), and
external zone (ZE)
Fibers coursing through the ZI are
vasopressin positive
Fibers terminating in the ZE in close
association to portal capillaries (PC)
are TRH-positive
Vasopressin- Somatostatin
Vasopressin
Somatostatin
Output
Sympathetic division
Output
Parasympathetic division
Output
projections from the PVN
Hypothalamus
• Subdivided in three longitudinal zones
– Periventricular, medial and lateral
• Rostrocaudally divided in
• anterior, tuberal and posterior (mammillary) part
• Based on patterns of connectivities
subdivided in
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Neuroendocrine motor zone: contains the endocrine motor neurons relted to posterior and
anterior pituitary
Circadian timing generator: organizes the temporal structure of hypothalamis functions
Pattern generating network: coordinates endocrine and autonomic patterns
Behavior control column: regulation of defensive, ingestive (nutrition and fluid balance),
reproductive and thermoregulatory behavior.
Sagittal section
Frontal section
Frontal sections
Intermingling of nerve cells
A pair of photomicrographs illustrating the distribution
of oxytocin and vasopressin neurons in the human
paraventricular nucleus.. Scale = 250 μm.