The Hypothalamus and Human Nervous System: A Primer

The Hypothalamus and Human Nervous System: A Primer
by
Mark J Donohue
I reported in – “Multiple Chemical Sensitivity: An Introduction” - that multiple chemical sensitivity
(MCS) is a real physiological disorder with an unknown origin. However, numerous theories have been
proposed leaving one wondering where to start in their search for the root cause of MCS. I also
proposed that MCS could very well be the result of a dysfunctional hypothalamus, a structure found
deep in the middle of the brain in an area referred to as the limbic system. Thereby, making the study of
the brain and nervous system a good place to start in one’s search for a cause.
I also realize that many people may be completely unfamiliar (as I once was) with these anatomical
terms and their physiological roles in the body. This can be a major obstacle; therefore, if one wishes to
understand the dysfunctional hypothalamus theory or any of the other neurologically based theories, it
is imperative that they have a basic understanding of the human nervous system.
Luckily, they don’t have to spend hours looking through
pages and pages of Human Anatomy textbooks. Nor do
they have to spend hours on line looking at one
Neurology website after another. I’ve already done this
for them and have written this report to give a quick bare
bones basic crash course on - The Hypothalamus &
Human Nervous System.
Introduction
The human nervous system is a collection of cells, tissues,
and organs. It is the most complex organ system in the
body. Its primary purpose is to: monitor internal and
external environments, integrate sensory information,
and coordinate voluntary and involuntary responses of
the many organ systems.
The human nervous system can be split into two separate
divisions: the central nervous system (CNS), consisting of
the brain and the spinal cord and the peripheral nervous
system (PNS), consisting of all the nerves of the body
“outside” of the central nervous system.
Image: The central nervous system (brain and spinal cord) and the peripheral nervous system (in green)
The Central Nervous System (CNS)
The central nervous system (CNS) is the core of our existence by acting as the command center of the
body. It interprets incoming sensory information, and then sends out instructions on how the body
should react. The CNS consists of two major parts: the brain and the spinal cord.
The brain is made up of approximately three pounds of soft tissue. This soft tissue is a conglomeration
of several structures and is composed of 100 billion nerve cells called neurons which make a million
trillion connections.
The largest structure in the brain is called the cerebrum and is the site where conscious thought and
intellectual function originate. The cerebrum is made up of two large masses called cerebral
hemispheres which are connected deep in the middle by nerve fibers called the corpus callosum. The
hemispheres are covered by a thin layer of gray/grey matter known as the cerebral cortex. The cortex
in each hemisphere of the cerebrum is between 1 and 4 mm thick, is filled with neurons and supportive
non-nerve cells called neuroglial cells. The inner portion of the cerebrum is mostly white matter filled
with nerve fibers called axons. These nerve fibers are coming from and going to the cerebral cortex
carrying electrical impulses and are covered by a protective fatty substance called myelin.
Image: Shows areas of gray and white matter in the brain
The cortex is further divide into four lobes, each being attributed to major body functions:
1) Frontal lobe – is involved in motor activity, speech and thought processes. It allows us to learn
by being able to focus on one single task for any length of time.
2) Parietal lobe – keeps us oriented not only to our surroundings but to our own body by
processing information about touch, taste, pressure, pain, heat and cold.
3) Occipital lobe – the visual lobe of the brain which receives and processes visual information
from our eyes.
4) Temporal lobe – receives auditory signals, process language and the meaning of words. Long
term and short term memories are also generated here.
The second largest structure of the brain called the cerebellum, is similar to the cerebrum in that it has
two hemispheres and has a highly folded surface or cortex. This structure controls motor coordination,
body movement, posture and balance.
Image: The brain with labeled structures
Located at the bottom most portion of the brain is a structure called the brain stem, which connects the
cerebrum with the spinal cord. The brain stem controls breathing, heart rate, blood pressure and
digestion and is made up of the midbrain, pons, and medulla oblongata.
The spinal cord runs along the spine and acts as a major highway for the passage of sensory impulses to
the brain and of motor impulses coming from the brain. The spinal cord has a central canal, which is a
narrow internal passageway filled with cerebrospinal fluid. And the spinal cord contains approximately
one hundred million neurons.
Deep within the core of the brain there exists a series of caverns called ventricles. Like most caverns, the
ventricles connect to each other by way of several narrow passages, each having its own special name.
Cerebrospinal fluid is also found circulating through the ventricles until it escapes to the outside where it
then circulates over the surface of the brain and is absorbed back into the blood. The cerebrospinal fluid
acts, not only as a cushion for the spinal cord and brain, but as a transport mechanism for important
chemicals, hormones and electrolytes.
The Peripheral Nervous System (PNS)
The peripheral nervous system (PNS) is the part of the nervous system “outside” of the central nervous
system (CNS). It consists mainly of nerves that extend from the brain and spinal cord to areas in the rest
of the body. Meaning all sensory information and motor commands are carried by the nerves of the
peripheral nervous system. All the nerves of the peripheral nervous system can be categorized as either:
A. Cranial nerves - 12 pairs of nerves which originate from the brain. These nerves are numbered using
roman numerals for identification. Some cranial nerves are sensory nerves, some are motor nerves
and some have both components. Each nerve follows a defined path and serves a specific region of
the body.
Image: 12 pairs of cranial nerves with associated motor and/or sensory function
B. Spinal nerves - 31 pairs of nerves
originating from the spinal column.
There are four main groups of spinal
nerves each serving a specific region of
the body: 1) cervical nerves (C1 – C8)
are nerves in the neck that supply
movement and feeling to the arms,
neck and upper trunk. 2) thoracic
nerves (T1 – T12) are nerves in the
upper back that supply the trunk and
abdomen area. 3) lumbar nerves (L1 –
L5) and 4) sacral nerves (S1 – S5) both
are nerves in the lower back that
supply the legs, bladder and bowel.
As mentioned, the cranial and spinal
nerves serve specific areas of the body and
perform specific functions. The functions
of these nerves are categorized into two
general sub-divisions of the peripheral
nervous system. They are:
1) The somatic nervous system – which
consists of nerves that go to the skin and
muscles and are involved in conscious
activities or voluntary movements.
2) The autonomic nervous system – which
consist of nerves that connect to organs
such as the heart, stomach, intestines and
mediates unconscious or involuntary activities
in the body. The autonomic nervous system is
further sub-divided into:
Image: Spinal nerves
a) The sympathetic nervous system which is involved in the “fight or flight” response causing
stimulation in tissue metabolism and increased alertness.
b) The parasympathetic nervous system which is antagonistic (operates in reverse) to the
sympathetic nervous system, and is involved in relaxation, the conservation of energy and
promotes sedentary activity such as digestion.
The Neuron
The cells making up the human nervous system are called neurons or nerve cells. They are special cells
capable of receiving a stimulus, transmitting that stimulus throughout their length of the cell, and then
delivering that stimulus to other cells next to them. They are the basic units of the nervous system and
the human body contains about 200 billion neurons, half of which are located in the brain.
A neuron consists of three main parts: the cell body, dendrites, and an axon. The dendrites and axons
are both referred to as nerve fibers.
The cell body, also called the soma, contains the nucleus, mitochondria and is the metabolic center of
the neuron. It contains all of the
necessary organelles for the
second by second operation of the
nerve cell.
Extending out from the cell body
are hair-like threads branching out
like a tree called dendrites.
Dendrites are the points through
which signals from adjacent
neurons enter a particular neuron.
Since each neuron contains many
dendrites, a neuron can receive
signals from many other
surrounding neurons, hundreds if
not thousands of other neurons.
Another extension, this one on the
opposite side of the cell body, is a
single elongated tail like extension
called an axon. Axons have the opposite
function of dendrites - they carry
Image: A typical neuron
nerve impulses away from the
cell body. Axons vary in length and diameter. Some, such as those in the central nervous system, are
short and are no longer than 0.01 inch. Others, such as those in the peripheral nervous system, can be 3
feet long. The axon ends in a cluster of branches called terminal branches or axon terminals.
Most long axons are surrounded by a white, fatty insulating material called myelin. The tube like
covering formed is known as a myelin sheath. It serves the same kind of function as the wrapping on a
telephone line or an electrical cable. It protects the axon and prevents electrical impulses traveling
through it from becoming lost.
There are three types of neurons:
1) Sensory neurons – form the afferent (going toward the CNS) division of the peripheral nervous
system. Sensory neurons receive information from sensory receptors that monitor the external
and internal environments. They then relay the information to the central nervous system.
Sensory neurons have long dendrites and short axons.
2) Motor neurons – form the efferent (going away from the CNS) division of the peripheral nervous
system. They have long axons and short dendrites and transmit messages from the central
nervous system to tissues, organs and glands.
3) Inter-neurons – are located entirely within the central nervous system. Inter-neurons connect
neuron to neuron and are responsible for the distribution of sensory information and the
coordination of motor activity.
Images:
Above - A typical neuron cell body with dendrites and axon.
Left – A forest of neurons: this image shows a minute fraction of
the cells and connections within the cortex.
Neuroglial Cells or Glial Cells
Neuroglial or Glial cells make up ninety percent of the brain’s cells. Glial cells are in direct contact with
neurons however, they do not carry nerve impulses. Instead these cells perform many important
functions such as digesting parts of dead neurons, manufacturing myelin and providing physical and
nutritional support for neurons. There are several types of glial cells. Four types of which are found in
the central nervous system (CNS):

Astrocytes - are the largest and most common type found in the CNS. Astrocytes secrete
chemicals vital to the maintenance of the blood brain barrier and create structural support for
the neurons of the CNS.

Oligodendrocytes - create the myelin sheath on axons in the CNS. They have thin extended tips
which wrap around axons and create a membranous sheath of insulin made of myelin.

Microglia – are the smallest and rarest type of glial cell found in the CNS. They are phagocytic
cells derived from white blood cells that engulf cellular waste and pathogens.

Ependymal – line the central canal of the spinal cord and ventricles in the CNS.
Image: Glial cells of the central nervous system
Two types of glial cells are found in the peripheral nervous system (PNS):

Satellite cells – surround and support neuron cell bodies in the PNS much like astrocytes in the
CNS.

Schwann cells – produce the protective myelin sheath which surrounds axons of the PNS, much
like oligodendrocytes in the CNS.
Another difference between the central nervous system (CNS) and the peripheral nervous system (PNS)
is when it comes to gray and white matter.
Gray or grey matter refers to a collection or bundle of neuron cell bodies. When found in the CNS grey
matter is called a center. Or a center with a distinct boundary is called a nuclei or nucleus. The most
complex integration centers or nuclei in the brain are referred to as higher centers.
White matter refers to a collection or bundle of neuron axons. In the CNS axons that share common
origins, destination and function are called tracts. Tracts in the spinal cord form larger groups called
columns. In the PNS these bundles of axons are simply called nerves (i.e. cranial and spinal nerves).
Neurotransmission
A sensory stimuli triggers an impulse or signal to be generated within the neuron. This signal, carried
down the neuron, is transmitted in the form of an electrical current called an action potential or nerve
impulse. This electrical impulse, on the order of 50-70 millivolts, travels down the axon at speeds up to
200 miles per hour. Sodium (Na+) and Potassium (K+) are the main ions involved in this process which
occurs in one direction only.
Image: Axon showing nerve impulse/action potential
Once the signal reaches the end tip of the axon called the terminal button or bulb, the electrical portion
of the signal can no longer continue its transmission due to a spacious gap called the synapse or
synaptic cleft.
Synapses occur between the axon of a pre-synaptic neuron and a dendrite or cell body of a postsynaptic neuron. At a synapse, the end of the axon is 'swollen' and there you find membrane sacs called
synaptic vesicles. Theses vesicles contain transmitter chemicals and mitochondria (which provide ATP energy) to make more transmitter chemicals. Because the pre and post neurons do not actually come in
contact and that the nerve impulse cannot be transmitted directly, the signal transmission is now
continued through the release of transmitter chemicals from the synaptic vesicles into the synaptic cleft.
These chemicals are called neurotransmitters.
The chemical transfer of information across the synapse is called neurotransmission or synaptic
transmission and takes place through out the brain trillions of times per second.
Neurotransmitters
The study of neurotransmitters is highly complex with new information being discovered daily. With that
said most all neurotransmitter molecules undergo a similar cycle of use involving:

Being manufactured in the cell body.

Being transported along the axon to the terminal bulb of the neuron, where they are enclosed in
small membrane bound sacs - vesicles.

When a nerve impulse arrives at the axon terminal the vesicles release the neurotransmitters into
the synaptic cleft.

Neurotransmitters travel across the synaptic cleft and bind with receptors on the postsynaptic cell.

The neuron will continue to fire as long as the neurotransmitter remains in the synaptic cleft and
therefore must be removed and/or degraded. This is done by either:
a) Re-uptake – where the neurotransmitter is reabsorbed back into the neuron bulb of the presynaptic neuron that released it in the first place.
b) Be broken down by special enzymes – deactivating the neurotransmitter and changing it into a
harmless by-product.
Image: Neuron synapse with identified structures
The primary function of a neurotransmitter is to either:
1. Inhibit the transmission of a nerve impulse – inhibitory neurotransmitters.
2. Excite or stimulate the postsynaptic membrane – excitatory neurotransmitters.
3. Modulate or modify the release of a neurotransmitter – neuromodulators.
Many neurotransmitters fall neatly into one of these functions listed above. For example glutamate is
the most common excitatory neurotransmitter in the brain, while GABA is the major inhibitory
neurotransmitter in the brain. However, other neurotransmitters may have all these functions. This is
because the effect on the postsynaptic cell depends entirely on the properties of the receptor. This
means that a specific neurotransmitter released at a particular site in the body might cause an
excitatory response. While the same neurotransmitter released at a different site in the body might
cause an inhibitory response.
The total number of neurotransmitters is not known, but it is well over 100. Because of this diversity
there are several ways that neurotransmitters can be categorized. The most common way is to divide
them into two major categories: small-molecule neurotransmitters and large-molecule
neurotransmitters also referred to as neuropeptides or peptide neurotransmitters. Below is a list of the
more common neurotransmitters with a description of their functions.
Small-Molecule Neurotransmitters
Mediate rapid synaptic actions and use the re-uptake mechanism to recycle the neurotransmitter.
Small-molecule neurotransmitters are further subdivided into several classes of neurotransmitters:
1) Acetylcholine (Ach) – is in a class all by itself. Is generally an excitatory neurotransmitter, but in
some sites can be inhibitory. Is the main neurotransmitter in the PNS and is made from choline. It
controls muscle contraction, heart rate, digestion, secretion of saliva and bladder function. In the
CNS, it is involved in attention, learning, memory, anger, aggression and sexuality. Neurons that
synthesize and release ACh are termed cholinergic neurons.
2) Amino acids are the building blocks of proteins and peptides. There are approximately 20 common
amino acids, several of which also act as neurotransmitters. These amino acid neurotransmitters are
the most prevalent neurotransmitters in the brain (CNS).

Aspartate – excitatory neurotransmitter - works closely with glutamate in stimulating the
NMDA receptors.

Glutamate – excitatory neurotransmitter - is the most common neurotransmitter in the brain
and is vital for learning and forming long-term memory. Is the major neurotransmitter in the
hypothalamus.

Gamma aminobutyric acid (GABA) – inhibitory neurotransmitter - is a well-known inhibitor of
pre-synaptic transmission in the CNS and is involved in relaxation. GABA is formed from
glutamic acid and astrocytes. Neurons that secrete GABA are termed GABAergic

Glycine –inhibitory neurotransmitter - it participates in the processing of motor and sensory
information that permits movement, vision, and audition. In addition, glycine modulates
excitatory neurotransmission by potentiating (increase the effect of) the action of glutamate at
the NMDA receptor.

Taurine – inhibitory neurotransmitter – modulates excitatory transmission by preventing the
harmful effects of excess glutamate. It also maintains fluid balance, healthy sleep and calmness.
3) Monoamines – neurotransmitters grouped together with a common molecular structure (contain an
amino group attached to an aromatic ring).
a) Catecholamines – a sub-group with a common molecular structure (contain a catechol group).
o
Dopamine – generally an excitatory neurotransmitter, but in some sites can be inhibitory derived from the amino acid tyrosine. It controls arousal levels in many parts of the brain
and is involved in controlling movement and posture. It also modulates mood – pleasure,
attachment, love and is involved in addiction.
o
Epinephrine / Adrenaline – excitatory neurotransmitter - derived from the amino acid
tyrosine. It is usually thought of as a stress hormone released by the adrenal glands, but it
also acts as a neurotransmitter in the brain.
o
Norepinephrine / Noradrenaline – generally an excitatory neurotransmitter, but in some
sites can be inhibitory - derived from the amino acid tyrosine. It plays an important role in
the sympathetic nervous system which is involved in physical and mental arousal, alertness
and co-ordinates the ‘fight or flight’ response.
b) Indoleamines – a sub-group with a common molecular structure (contain indoleamine).
o
Serotonin – generally an inhibitory neurotransmitter, but in some sites can be excitatory derived from the amino acid tryptophan. It has a profound effect on mood and anxiety.
When we have enough serotonin we feel emotionally stable. It is also involved in the
regulation of sleep, pain perception, body temperature, blood pressure and hormonal
activity.
o
Melatonin – inhibitory neurotransmitter – derived from the amino acid tryptophan and
released from the pineal gland. Involved in regulation of arousal and sleep cycle.
o
Histamine – excitatory neurotransmitter - derived from the amino acid histidine and acts in
mediating arousal and attention. It also acts as a pro-inflammatory signal released from
mast cells in response to allergic reactions or tissue damage. Histamine is also an important
stimulant of hydrochloric acid secretion by the stomach through histamine H2 receptors.
Large-Molecule Neurotransmitters
Also referred to as neuropeptides or peptide neurotransmitters - are compounds consisting of two or
more amino acids chained together by what is called a peptide bond. Neuropeptides are wide spread in
the human nervous system and function as both neurotransmitters and hormones.
Similar to the small-molecule neurotransmitters, neuropeptides also have both excitatory and inhibitory
actions, though their main role is that of neuromodulators. However, unlike the rapid synaptic action of
the small-molecule neurotransmitters, neuropeptides tend to modulate slower, ongoing synaptic
functions. Their effects last longer.
Presently there are over 100 neuropeptides. Neuropeptides are degraded or broken down in the
synaptic cleft by special enzymes – no reuptake. And they are divided into two sub-categories:
1) Opioids – neurotransmitters that bind to the opioid receptors and create a morphine-like response
in the body (relieves pain, feelings of pleasure). Morphine is the active agent in opium (poppy tears).

Endorphins - are produced by the pituitary gland and the hypothalamus. They bond to opioid
receptors in the nervous system to relieve pain. Endorphins moderate appetite, release sex
hormones, decrease stress, and create euphoria or happiness. There are over 20 types of
endorphins.

Enkephalin – inhibitory neurotransmitter - regulates pain in the body and serves as a “natural
pain killer”.

Dynorphins – Involved in pain control and in the regulation of immune response. It’s also
involved in promoting emotional balance, enhancing mental activity and reducing obsessivecompulsive behavior. Highest concentrations are found in the hypothalamus, midbrain and
spinal cord.
2) Non-Opioids

Substance P – excitatory neurotransmitter - involved in the transmission of pain impulses from
the PNS to the CNS and may also be involved in nerve regeneration.

Oxytocin - stimulates milk ejection during lactation, uterine contraction during birth, and is
released during sexual orgasm in both men and women.

Neuropeptide Y – secreted by the hypothalamus to stimulate eating.

Angiotensin II - stimulates thirst, may regulate blood pressure in the brain, and promotes
release of aldosterone which increases the rate of salt and water re-absorption in the kidneys.

Vasopressin – also called antidiuretic hormone (ADH) or arginine vasopressin (AVP) – constricts
blood vessels, raises blood pressure and reduces excretion of urine.

Corticotropin releasing hormone – secreted by the hypothalamus in response to stress.
The Receptor
After release into the synaptic cleft, neurotransmitters and neuropeptides interact with specialized
proteins called receptors that are embedded in the post-synaptic membrane. These receptors are also
called ion channels or ion channel receptors. An Ion is simply an atom or molecule with an electric
charge, either positive or negative (i.e. sodium, potassium, calcium, chloride). An Ion channel is a “pore”
in the neuron’s cell membrane which allows ions to pass in or out of the cell body. Ion channels are able
to control the passage of ions by means of a gate. There are several types of ion channels that are
classified according to their type of gating mechanism:



Voltage-Gates – open or close in response to change in charge across the cell membrane
Ligand-Gates – open or close in response to binding of a small signaling molecule called ligand.
Stretch-Gates – open their pores in response to mechanical deformation.
When these channels open, sodium and/or calcium enter the cell and depolarize it. This results in the
initiation of another action potential/nerve impulse, causing the neuron to fire.
Image: Gated ion channel being opened by neurotransmitter
The neurotransmitter – receptor system acts much like a lock and key. The receptor is the lock and the
neurotransmitter is the key. Only certain keys will open certain locks and so to, only certain
neurotransmitters will open certain receptors. For example, the neurotransmitter glutamate will only fit
into and open a glutamate receptor. This same neurotransmitter will be unable to fit into an
acetylcholine receptor and therefore will be unable to open it. To complicate the issue even further,
there are many subtypes of receptors for each neurotransmitter (below is a partial list).
Chart: A partial list of the most common neurotransmitters and their related receptor subtypes
It is beyond the scope of this report to describe the many types of receptors and receptor subtypes.
However, for the purpose of this report and because glutamate is the major neurotransmitter in the
hypothalamus we will focus primarily on the glutamate receptor and its subtypes. The neurotransmitter
glutamate has at least three subtypes of glutamate receptors all found on the postsynaptic cell
membrane and each one named after the chemical that stimulates them:
1) N-methyl-D-aspartate (NMDA)Receptor
2) Quisqualate Receptor
3) Kainite Receptor
The NMDA receptor is the most common of the three types of glutamate receptors found on neuron
membranes in the brain. It acts as the gate keeper of a special ion channel called a calcium channel. This
channel regulates the entry of calcium into the inside of the neuron. The channel is opened when the
neuron is activated by the neurotransmitter glutamate, the specific key. The neurotransmitter aspartate
can also open this channel.
However, the NMDA receptor is unique in that more than one key is required to activate it. The other
locks on the membrane include a zinc receptor, a magnesium receptor and a glycine receptor. Zinc can
only lock the gate – it closes the calcium channel tight. Magnesium also locks the gate, but not as tight
as zinc. Magnesium can easily be displaced if the neuron fires. Glycine, on the other hand is necessary
for the calcium channel to open. As a matter of fact it has been shown that if glycine is removed from a
culture of nerve cells, no concentration of glutamate can make the nerve cell fire. But when glycine is
added the neurons become much more sensitive to firing.
The Limbic System
Originally, we identified the major structures of the brain to be the cerebrum, cerebellum, brain stem
and spinal cord. There are also within the brain several smaller structures. For the purpose of this report
we will concentrate on a couple of these structures that are found deep within the cerebrum and
collectively make up the limbic system.
The limbic system is often referred to as the “emotional brain” because its main function is to: a)
establish emotional states and related behavioral drives. b) link the conscious, intellectual functions of
the cerebral cortex with the unconscious and autonomic functions of the brain stem and spinal cord. c)
store and retrieve long-term memory.
It is important to note - the limbic system is not a structure, but a series of nerve pathways between a
complex set of structures. It should also be noted that there is a lack of agreement about exactly which
structures should be included in a description of the limbic system. The limbic system structures related
to this report are:
 Thalamus – a large dual lobed mass of gray matter (neurons) found deep in the brain just above
the brain stem. It acts as an integration unit that performs complex functions relaying all
sensory signals (except for olfaction) to and from the spinal cord and the cerebrum.
 Hypothalamus – controls many functions in the body by acting as an interface between the
limbic, endocrine and autonomic nervous systems. The hypothalamus is covered in more detail
below.
 Hippocampus – plays a significant role in the formation of long-term memories and is very
susceptible to damage from disease, anoxia (loss of oxygen) and environmental toxins. The
major outputs of the hippocampus are to the cortex and to the hypothalamus.
 Amygdala – serves in attaching emotional significance to perceived stimuli and therefore is
considered the emotional center of the brain. It is strongly associated with the emotions of fear
and anxiety. As a whole the amygdala is highly interconnected with the hippocampus and the
hypothalamus and because of these connections the amygdale is also involved in the
processing, storing and retrieving of memories. It also receives a rich supply of signals from the
olfactory system (smell).
 Olfactory System (smell) – it has been said that the limbic system, in part, evolved out of the
olfactory bulb. Axons leaving each olfactory bulb (in nose) travel along the olfactory tract to
reach the olfactory cortex (in the medial temporal lobe) and the amygdala. From there the
sensory information is projected to the hypothalamus.
Image: The limbic system with labeled structures.
The Hypothalamus
The hypothalamus is a small structure, about the size of an almond and is found deep in the center of
the brain. It is located below the thalamus and just above the brain stem.
Despite its size, the hypothalamus serves a vital role in the regulation of homeostasis – which is to
maintain internal metabolic equilibrium. The hypothalamus does this by linking the nervous system to
the endocrine system via the pituitary gland. Or in other words the hypothalamus regulates all
endocrine hormone levels as well as the autonomic nervous system.
Some of the homeostatic functions the hypothalamus regulates are:
 Metabolism - all of the energetic reactions that take place in our cells.
 Circadian rhythms or “biological clock” - biological events that repeat themselves at regular
intervals, i.e. the sleep – wake cycle.
 Heart rate and blood pressure
 Thermoregulation - body temperature
 Fluid and electrolyte balance
 Hunger, thirst and digestion
 Sexual behavior, arousal and reproduction
 Emotions and moods – pleasure, rage
 Immunity
 Memory
 Sympathetic and parasympathetic balance
This small structure is composed of even tinier structures called nuclei. As described earlier, nuclei are
clusters of tightly bundled neurons and the hypothalamus is comprised of a number of these nuclei.
Each nuclei is responsible for a specific function in the body and are found divided up into four regions in
the hypothalamus.
1) Preoptic Region:
o Medial Preoptic Nuclei – controls water intake, bladder contraction, blood pressure,
and heart rate
2) Supraoptic (anterior) Region:
o Supraoptic Nuclei – controls the release of oxytocin, vasopressin (ADH – antidiuretic
hormone), and corticotrophin releasing hormone (CRH). Also water conservation.
o Paraventricular Nuclei – controls same functions as supraoptic nuclei (above).
o Suprachiasmatic Nuclei – receives retinal inputs and projects to the pineal gland further
controlling circadian rhythms / “biological clock”.
o Anterior Nuclei – involved in thermoregulation (body temperature).
3) Tuberal (middle) Region:
o Lateral Hypothalamic Area – “feeding center”(urge to eat), thirst and hunger
o Ventromedial Nuclei - “satiety center”(urge to stop eating), aggression, “hypothalamic
rage”, neuroendocrine control
o Infundibular or Arcuate Nuclei – controls endocrine function via releasing
factors/hormones to the pituitary gland. This nuclei is the most sensitive to MSG toxicity
and has intimate connections to other nuclei (supraoptic and paranentricular).
o Dorsomedial Nuclei – involved in feeding, rage, gastrointestinal tract stimulation.
4) Mammillary (posterior) Region:
o Mammillary Body Nuclei – involved in memory.
o Posterior Nuclei – controls thermoregulation (body temperature) blood pressure and
pupil dilation.
Image: Nuclei of the hypothalamus
The hypothalamus and its nuclei maintain homeostasis by first processing the neural stimulation from a
variety of inputs both externally and internally. These inputs can come directly from the smell, taste,
visual and somatosensory systems (sensations that arise from the skin and body). Or the hypothalamus
can receive highly processed sensory information from the other limbic system structures
(hippocampus, amygdala).
In addition, the hypothalamus has the most rich and abundant blood supply in the brain. This blood flow
is constantly being monitored by the receptors within the hypothalamus (i.e. thermoreceptors,
osmoreceptors). This is done to measure the temperature, sugar, mineral and hormone levels within the
blood. Unlike other areas in the brain, the hypothalamus is able to perform this function because there
is no protective blood brain barrier (see below). This also leaves the hypothalamus vulnerable to toxic
substances in the blood.
Once the information from neural stimulation has been received and processed the hypothalamus is
then able to exert its control over many of the body’s functions via two major outputs.
1) The autonomic nervous system – the hypothalamus projects neural signals, via axons, to the
medulla (brain stem) and spinal cord where the cells that drive the autonomic nervous system
are located. This includes both the sympathetic and parasympathetic nervous systems. Thereby
controlling things like blood pressure, heart rate, breathing, digestion, sweating, etc.
2) The endocrine system - the hypothalamus controls the endocrine system by controlling the “the
master gland” – the pituitary gland. The hypothalamus masters “the master gland” by:
a) Projecting neural signals, via axons, to the posterior pituitary gland where oxytocin and
vasopressin (neuropeptides) is secreted.
b) Projecting neural signals, via axons, to the base of the pituitary where releasing
factors/hormones are emptied into the capillary system of the anterior pituitary. These
releasing factors induce the anterior pituitary to secrete at least six different hormones into
circulation.
c) Directly controlling autonomic outputs to many peripheral endocrine tissues (glands), which
further regulate their secretion.
The Blood Brain Barrier
The brain is a chemical factory which depends on careful quality control for its operation. The amounts
of these chemicals used, to transmit signals, is infinitesimal. The tiniest fluctuations in these
concentrations can result in dramatic disruptions of brain function.
Therefore, because of the extreme sensitivity of the brain and because the brain receives the same
blood that flows through the body, which contains a variety of harmful foreign substances, a means of
protecting the brain evolved called the blood brain barrier (BBB). The major function of the BBB is to
maintain a constant environment (homeostasis) for the brain by protecting it from foreign substances
such as viruses, bacteria and now man-made chemicals. As well as shielding it from neurotransmitters
and hormones.
In the rest of the body outside the brain, the walls of blood vessels are made up of endothelial cells
which are loosely packed together. This allows soluble chemicals to pass through the cell walls to the
various tissues. However, in the brain, endothelial cells are packed together more tightly with what are
called tight junctions. These tight junctions are what form the blood brain barrier. And it is these tight
junctions that block out potentially harmful substances while allowing in vital substances (nutrients) that
are needed by the brain (oxygen, sugars, etc.). Nutrients are able to cross the blood brain barrier by
means of special transporter proteins, while astrocytes surround the endothelial cells of the blood brain
barrier to provide biochemical support.
Image: Blood brain barrier with tight junctions showing the different transport systems.
Circumventricular Organs (CVOs)
After reviewing the information about the blood brain barrier it is important to note that there are areas
in the brain where the BBB is more porous. The organ structures that border these areas are called
circumventricular organs(CVOs). These organs are found at distinct sites around the margins of the
ventricles. You will recall that ventricles are caverns within the brain that are filled with cerebrospinal
fluid and connect with the central canal of the spinal cord.
Unlike the vascular system in the rest of the brain, the blood vessels in CVOs have fenestrated or
perforated capillaries that allow relatively free passage of larger molecules such as proteins and peptide
hormones. Thus, neurons and glial cells that reside within the CVOs have access to these
macromolecules. In addition to the distinct nature of the vessels themselves, the CVOs have an
unusually rich blood supply.
These factors are needed so CVOs can directly sense and monitor the concentrations of various
compounds in the blood stream without the need for specialized transport systems. In addition, several
of the CVOs have major projections to hypothalamic nuclear groups that regulate a variety of different
hormones, neurotransmitters and cytokines to maintain the body’s homeostasis.
Image: Circumventricular organs
Thus, CVOs serve as a critical link between peripheral metabolic cues, hormones, potential toxins and
cell groups within the brain that regulate coordinated endocrine, autonomic, and behavioral responses.
Or in other words CVOs act as integrators or relay points between the body and the CNS. The
circumventricular organs (CVOs) are:
 Medial eminence - the median eminence is located adjacent to several neuroendocrine and
autonomic regulatory nuclei of the hypothalamus. These nuclear groups include the infundibular
or arcuate, ventromedial, dorsomedial, and paraventricular nuclei. Therefore, the medial
eminence’s role is to act as a link between the hypothalamus and the anterior pituitary gland.
Experimental evidence suggests that the median eminence is a portal of entry for hormones
such as leptin (involved in appetite and metabolism).
 Posterior pituitary (neurohypophysis) – serves as a reservoir for neurohormones vasopressin,
oxytocin, and neurophysin (role unknown).
 Organum Vasculosum of the Lamina Terminalis (OVLT) - OVLT is surrounded by cell groups of
the preoptic region of the hypothalamus which regulates a diverse array of autonomic
processes. In addition the OVLT also has a restricted range of projections into other areas of the
hypothalamus which include the paraventricular and supraoptic nuclei, the dorsomedial
hypothalamic nucleus, and the lateral hypothalamic area.
 Subfornical organ (SFO) - This CVO critically regulates fluid homeostasis and contributes to
blood pressure regulation. Consistent with these functions, the SFO has receptors for
angiotensin II and the vasodilator - atrial natriuretic peptide (ANP).The SFO is thought to
regulate fluid homeostasis because of its specific and massive projections to key hypothalamic
regulatory sites. Notable among these are the inputs to oxytocin and vasopressin neurons in the
supraoptic and paraventricular nuclei. In addition, a dense supply of nerves can be found
traveling from the SFO to the preoptic region of the hypothalamus and other hypothalamic sites
including the lateral hypothalamus.
 Area Postrema - The best-described physiologic role of the area postrema is the coordinated
control of blood pressure. Due to the area postrema containing binding sites for angiotensin II,
AVP, and atrial natriuretic peptide. The area postrema also receives direct input from several
hypothalamic nuclei. Finally, the area postrema is thought to be critical in the detection of
potential toxins and can induce vomiting in response to foreign substances and therefore is
known as the “vomiting center”.
 Pineal gland – The metabolism of the gland exhibits high-amplitude circadian rhythms in the
synthesis and secretion of melatonin with peak production during the dark period.
 Subcommissural Organ – the physiologic role of the SCO is largely unknown.
 Habenula – the physiologic role of the habenula is largely unknown.
One final note - this monitoring system evolved long before mankind entered into the modern industrial
age. Simply put the circumventricular organs (CVOs) are now continuously exposed to a toxic soup of
chemicals flowing through the blood stream. This new and constant exposure thus makes the sensitive
CVOs susceptible to damage and thereby possibly causing a breakdown in the body’s regulation of
homeostasis.
References
Anatomy and Physiology for Emergency Care
By Martine, Bartholemew, Bledsoe
Pearson Education Inc. 2008
Principles of Human Anatomy
By Gerard J Tortera
John Wiley and Sons Inc. 2002
Textbook of Medical Physiology
By Guyton and Hall
Elsevier Inc. 2006
th
Williams Textbook of Endocrinology, 11 edition
By Henry Kronenberg
Elsevier Inc. 2008
WWW - dozens and dozens and dozens of sites pertaining to subject of the human nervous system
Google Images – all images came from Google images