physiology of brain

8/2/2019 Physiology of Brain

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Brain Physiology

By: Mark Bancroft, MA

Part One: The Major Structures of the Brain.

The human brain is a mass of pinkish-gray tissue containing a neural network

involving approximately 10 billion nerve cells, called neurons. Glial cellsserve as the brain's support system, in addition to blood vessels and secretory

organs. Weighing in at a mere three pounds, the brain operates as the central

control system for movement, sleep, hunger, and thirst. It controls nearly

every vital activity necessary for survival. Emotions are controlled by the

brain: anger, fear, joy, love, elation, contentment, and happiness find their

origin inside the brain. Furthermore, the brain receives and interprets the

multitude of signals being sent by other parts of the body and the outside

environment. There are three major divisions of the brain: the forebrain,

midbrain, and hindbrain.

A. Forebrain:

For anatomical study the forebrain is divided into two subdivisions: the

telencephalon and the diencephalon. The primary structures of the

telencephalon include the cerebral cortex, basal ganglia, and the limbic

system. The diencephalon includes the thalamus and the hypothalamus.

Telencephalon:

Cerebral Cortex: Likened to the bark on a tree, the cerebral cortex surrounds

the cerebral hemispheres. The cerebral cortex is the folded, convoluted tissue

commonly imagined when an image/thought of the brain is recalled from

memory. The folded, crumpled structure contains an enormous amount of

small and large grooves (sulci and fissures) and bulges (gyri). This type of

structure is beneficial for it greatly increases the overall surface are of the

cortex. In fact, because of the convoluted design the area of the cerebral

cortex is tripled!


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The cerebral cortex is commonly referred to as gray matter. This is based

upon the appearance of the cortex which, due to the predominance of cells

appears grayish brown. The neurons of the cerebral cortex are connected to

other neurons within the brain via millions of axons located beneath thecortex. This area is white in color due to the concentration of myelin; it is

often called white matter.

One of the most apparent visible features of the brain is the division between

the left and right hemispheres of the cerebral cortex. Through evolutionary

advances the functions of each hemisphere have evolved. Mental and

emotional differences between men and women are speculated to result from

different modes of functioning between the two hemispheres. In most cases

the left hemisphere is deemed the dominant half of the brain. This is due to itssuperior language abilities as well as its analytic, sequential.

In general terms it is well understood that the left hemisphere controls

linguistic consciousness, the right half of the body, talking, reading, writing,

spelling, speech communication, verbal intelligence and memories, and

information processing in the areas of math, typing, grammar, logic, analytic

reasoning, and perception of details. The right hemisphere is associated with

'unconscious' awareness (in the sense it is not linguistically based), perception

of faces and patterns, comprehension of body language and social cues,

creativity and insight, intuitive reasoning, visual-spatial processing, and

holistic comprehension. Communication between the two hemispheres takes

place through the corpus callosum, which, by the way, is more fully developed

in women than men- likely giving rise to women's intuition.

The surface of the cerebral hemispheres is divided into four lobes

corresponding to the names of the skull plates that protect them: thefrontal

lobe,parietal lobe, temporal lobe, and the occipital lobe. In addition to thesefour lobes, a fifth lobe exists called the insula. This lobe is internal and is not

visible from the surface of the brain.

The frontal lobes went through a tremendous evolutionary expansion 50,000

years ago. Subsequently, the capacities for long-term planning, goal

development, and the ability to override immediate gratification in favor for

future goals greatly expanded. The frontal lobes are sometimes associated

with what it means to be human. Absence of the frontal lobes typically results

in a person who is deemed emotionally shallow, listless, apathetic, andinsensitive to social norms. According to Candace Pert, "If God speaks to


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man, if man speaks to God, it would be through the frontal lobes, which is the

part of the brain that has undergone the most recent evolutionary expansion."

Furthermore, the frontal lobes exert a degree of control over the hypothalamus,

which controls the autonomic nervous system and endocrine system, as well as

organizes survival behavior. Control of movement is associated with the

frontal lobes via theprimary motor cortex located within this lobe.

The parietal, temporal, and occipital lobes are specialized for perception.

Within the parietal lobe is theprimary somatosensory cortex which receives

information pertaining to the senses of the body: touch, pressure, temperature,

and pain. Visual information is received by theprimary visual cortex located

within the occipital lobe. Hearing is processed in theprimary auditory cortex

within the temporal lobe. The central sulcus (fissure of Rolando) divides the

frontal lobe from the parietal lobe. The lateral fissure (fissure of Sylvius)

separates the temporal lobe from the overlying frontal and parietal lobes. Theparieto-occipital fissure separates the parietal and occipital lobes.

The corpus callosum is the primary connection between the left and right

hemispheres of the cerebral cortex. Connection between the two halves takes

place through axons that unite geographically similar regions of the two

cerebral cortices.

Basal Ganglia: The basal ganglia are a collection of subcortical nuclei

situated beneath the anterior portions of the lateral ventricles; they are

involved with the control of movement. Parkinson's disease has an effect upon

the basal ganglia resulting in poor balance, rigidity of the limbs, tremors,

weakness, and difficulty with initiating movements. Some anatomists

consider the amygdala (primary component of the limbic system) a part of the

basal ganglia given its location.

The Limbic System: The limbic system is a collection of brain structures

involved with emotion, motivation, multifaceted behavior, and memory

storage and recall. The hippocampus (sea horse)and the amygdala (almond),

along with portions of the hypothalamus, thalamus, caudate nuclei, and septum

function together to form the limbic system. [see question #4 for further

information].

Diencephalon:

The diencephalon is the second major division of the forebrain. The principle


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structures include the thalamus and hypothalamus.

Thalamus: The thalamus is the relay station for incoming sensory signals and

outgoing motor signals passing to and from the cerebral cortex. With theexception of the olfactory sense, all sensory input to the brain connected to

nerve cell clusters (nuclei) of the thalamus. The thalamus consists of two large

connected lobes. The massa intermedia serves as a bridge connecting the two

lobes of the thalamus. It is comprised of gray matter and is deemed a non-

critical part of the brain; absence of which is outwardly unnoticeable.

Hypothalamus: The hypothalamus is comprised of distinct areas and nuclei

which control vital survival behaviors and activities; such as: eating, drinking,

temperature regulation, sleep, emotional behavior, and sexual activity. It islocated just beneath the thalamus and lies at the base of the brain. The

autonomic nervous system and endocrine system are controlled by the

hypothalamus. The anterior pituitary glandis directly connected to the

hypothalamus via a special system of blood vessels. Neurosecretory cells

released by the hypothalamus act upon the anterior pituitary gland which then

secretes its hormones. Most hormones secreted by the anterior pituitary gland

control other endocrine glands. Because of this the anterior pituitary gland is

sometimes referred to as the Master Gland. Hormones of theposterior

ituitary glandare also governed by the hypothalamus.

B. Midbrain, The Mesencephalon:

Two primary parts comprise the midbrain : the tectum and the tegmentum.

Tectum: The primary structure of the tectum include the superior colliculi andthe inferior colliculi. The superior colliculi form part of the visual system.

The inferior colliculi are part of the auditory system. The structures appear as

four small bumps located on the brain stem. Function in mammals relates to

visual reflexes and reaction to moving stimuli.

Tegmentum: The tegmentum is situated below the tectum. The reticular

ormation, periaqueductal gray matter, and the red nucleus and substantia

nigra are part of the tegmentum. The reticular formation is comprised of more

than 90 nuclei and an interconnected neural network located at the core of thebrain stem. It receives sensory information and is involved with attention,


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sleep and arousal, muscle tonus, movement, and various vital reflexes.

The periaqueductal gray matter consists of neural circuits that control

sequences of movements constituting species-typical behavior. The rednucleus and substantia nigra are parts of the motor system. The red nucleus

serves as one of two major fiber systems bringing motor information from the

brain to the spinal cord. The substantia nigra affects the caudate nucleus via

dopamine-secreting neurons.

C. The Hindbrain:

Metencephalon:

Cerebellum (little brain): The cerebellum's primary function involves control

of bodily movements. It serves as a reflex center for the coordination and

precise maintenance of equilibrium. Voluntary and involuntary bodily

movements are controlled by the cerebellum. Visual, auditory, vestibular, and

somatosensory information is received by the cerebellum, as is information on

the movements of individual muscles. Processing of this information results

in the cerebellum's ability to guide bodily movements in a smooth and

coordinated fashion.

Pons: The pons appear as a large bulge in the brain stem between the

mesencephalon and the medulla oblongata. The pons contain a portion of the

reticular formation as well as nuclei believed important in the role of sleep and

arousal.

Myelencephalon:

The myelencephalon is comprised of one structure: the medulla oblongata

(oblong marrow). It is the origin of the reticular formation and consists of

nuclei which control vital bodily functions. The medulla oblongata is the

control center for cardiac, vasoconstrictor, and respiratory functions. Reflex

activities, including vomiting, are controlled by this structure of the hindbrain.

Appearing as a pyramid-shaped enlargement of the spinal cord, damage to this

area typically results in immediate death.


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Part Two: The Neuron:

A. Basic Neuron Description:

A neuron, also known as a nerve cell, is the information processing and

transmission device of the nervous system. They come in a variety of shapes,

sizes, and types. In the human body, certain neurons reach up to three feet

long. While differences exist between particular neurons given their

specialization, most neurons are comprised of four primary structures: the

soma; dendrites; axon; and terminal buttons.

Soma: The soma is the cell body of the neuron. It houses the nucleus and the

majority of cell components which sustain the life processes of the cell. The

shape of the cell body varies greatly between the different types of neurons.

Dendrites: The dendrites branch out from the soma resembling branches of a

tree (dendron is Greek for Tree). With the exception of sensory neurons, the

dendrites are the mechanism through which a neuron receives communication,

incoming information, from other neurons. Sensory neurons transmitinformation where the incoming signal is generated by specialized receptors in

the skin. Messages between two neurons are transmitted across the synapse, a

unction between the receiving dendrites of one neuron and the information

sending terminal buttons of another. Communication between neurons is a

one-way affair. Signals are sent out by one neuron through the terminal

buttons and received by the cell membranes of the receiving neuron.

Axon: The axon is a long, slender tube that carries information away from the

soma to the terminal buttons. Axons are usually covered by a myelinatedsheath. The axon carries a basic message called termed an action potential.

The action potential is a brief electrical/chemical event which starts at the end

of the axon near the soma and travels downward to the terminal buttons. The

action potential is consistent; I remains the same size and duration even

through axonal branches. Each branch of an axon receives a full charge.

As with the dendrites, axons come in different shapes. Furthermore, the three

principal types of neurons are classified by the manner in which their axons

and dendrites leave the soma. The most common type of neuron is themultipolarneuron which has one axon and many branches of dendrites.


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Bipolar neurons are depicted by having one axon and one dendritic tree, each

located at opposite ends of the cell body. Bipolar neurons are typically

sensory. They have a dendrite which receives information from a receptor

which gets sent onto the central nervous system informing it of external

events. Unipolar neurons, as found in the somatosensory system, consist of

one stalk containing terminal buttons at one end and a dendritic tree at theother.

Terminal Buttons: Most axons divide and split many times. At the ends of the

branches there are small knobs which are called terminal buttons. The

terminal buttons secrete neurotransmitters which affects the receiving cell.

Neurotransmitters can be either excitatory or inhibitory. The nature of the

neurotransmitter determines whether the receiving cell will send a message

down its axon and communicate with the connected to its terminal buttons. A

single neuron can receive information from hundreds of other neurons thuscreating an intricate neural network. Additionally, the terminal buttons of a

neuron can form synapses at the dendrites and/or cell body membranes of

adjacent neurons.

Internal Structure: The boundary of the nerve cell is defined by the cell

membrane. Within the membrane are protein molecules which serve special

functions for the cell. Some of the proteins detect substances outside the cell,

such as the presence of hormones, and pass the information onto the interior of

the cell. Other proteins serve as the cell's gatekeeper, allowing some

substances to pass into the cell while barring others. Some proteins functions

as transporters carrying certain molecules into and out of the cell.

At the center of the neuron is the nucleus which is round or oval and covered

by a nuclear membrane. Inside are the nucleolus and chromosomes. The

nucleolus manufactures small structures that are involved with protein

synthesis, called ribosomes. Genetic information is contained on long strands

ofdeoxyribonucleic acid(DNA) which make up the chromosomes. Whenportions of the chromosomes (genes) are active they cause the production of

messenger ribonucleic acid(mRNA). Messenger RNA exits the nuclear

membrane and attaches itself to ribosomes where the production of a specific

protein takes place. Proteins provide structure and serve as enzymes, directing

the chemical processes of a cell by controlling chemical reactions

Cytoplasm makes up the bulk of the cell. It is a jellylike, semiliquid substance

that fills the space within the membrane. Cytoplasm streams and flows, it is

not static. Contained within it are small, specialized structures essential for the


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makes them polarized. Polarization is caused by the free movement of

positively charged potassium ions through the cell membrane, andthe

retention of large, negatively charged molecules within the cell. An active

process keeps positively charged sodium ions outside the cell. Every cell has

this difference in electrical charge, but when a stimulating current is applied to

neuron, a unique event takes place. Stimulation of the neuron causespotassium ions to flow into the cell which reduces the negative charge; the

process is called depolarization. At a certain moment, the membrane changes

and the cell becomes permeable to sodium which quickly enters the cell

causing a positive charge to occur within the neuron. This event is called the

action potential.

Once the action potential is reached at one area of the neuron, it moves down

the axon via ion exchange at specific points called nodes of Ranvier. The size

of the action potential is self limiting. A high internal concentration of sodiumresults in the pumping out of potassium followed by sodium ions. This

restores the negative charge within the cell membrane causing the neuron to be

repolarized.

The entire process takes under 1/1000 of a second. The process can be

repeated after the refractory period. The attainment of action potential results

in the release of neurotransmitters at the terminal buttons. Thus, the electrical

processes of a neuron constitutes inner-cellular communication.

C. How the Neuron Works (chemically):

When the internal electrical signal of the neuron reaches the tip of an axon,

small presynaptic vesicles that contain neurotransmitters within the cell are

stimulated. The neurotransmitters are then released into the synaptic cleft, a

submicroscopic space between two neurons. The released neurotransmittersattach to specialized sites, receptors, on the surface of the adjacent neuron.

Once a neurotransmitter is received by the receptors of a neuron the cell

depolarizes and generates its own action potential. The stimulus of a

neurotransmitter has a limited duration. The duration of a stimulus from a

neurotransmitter is limited by two factors: the breakdown of chemicals in the

synaptic cleft, and the reuptake by the neuron which sent the

neurotransmitters. Neurons are now known to produce more than one type of

neurotransmitter.


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In addition to neurotransmitters, two other types of transmitter substances are

released by the terminal buttons of a neuron: neuromodulators and hormones.

Neuromodulators are more dispersed and travel farther than neurotransmitters.

They are released in larger amounts which allows them diffuse over a greaterarea of the brain, thus stimulating more neurons than do neurotransmitters.

Hormones are released into the extracellular fluid and travel about the body

through the bloodstream. Hormones can affect a neuron by stimulating

receptors on either the surface of the cell membrane or deep inside their

nuclei. Neurons containing the appropriate receptors are affected by the

presence of the hormones. Affected neurons can alter behavior.

Neurotransmitters, neuromodulators, and hormones affect nerve cells by

attaching to a specific region of the receptor molecule called the binding site.This is the site at which neurosubstances and the receptors of nerve cells

match one another; much like a lock and key. Whereas the neurosubstance

functions as the key, the receptors act as a lock- their duty is to allow only the

"right" kind of neurosubstance into the cell. Chemical that attach to a binding

site are called ligands. In their natural form ligands are the neurotransmitters,

neuromodulators, and hormones. However, other chemicals found outside the

body can function the same way as the natural ligands. Artificial ligands

include the substances of some plants and the venom of animals. Such ligands

can also be manufactured in a laboratory.

Pheromones can also function as artificial ligands. They are chemicals which

enter the environment through sweat, urine, or the secretion of specialized

glands. Their odor can be detected by receptors in the noses of other animals.

When pheromones contact such receptors, they typically affect the

reproductive behavior of other members of the same species. Pheromones are

known to attract potential mates, cause sexual arousal, inhibit aggression, and

alter the activity of the endocrine system.

D. How the Synapse Operates (inhibitory/excitatory):

Neurons communicate to each other by means of synapses; they release

neurotransmitters which diffuse across the synapse. Synapses are formed

where neurotransmitters diffuse across the gap between the terminal buttons of

one neuron and the membranes of adjacent neurons. The transmitter substance

can produce brief depolarizations or hyperpolarizations which are termed

postsynaptic potentials. Postsynaptic potentials may either increase ordecrease the firing of the axon in the postsynaptic neuron. The gap (synaptic


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cleft) between the terminal buttons of one neuron and the membrane of

another is very small, normally measuring a mere 200 angstroms wide. The

gap is filled with extracellular fluid through which the neurotransmitter

diffuses.

Synaptic vesicles are located in the cytoplasm of the terminal button, along

with mitochondria and a Golgi apparatus. The vesicles are small rounded

objects which generally come in two sizes: small and large. Small synaptic

vesicles are found in all terminal buttons and contain molecules of the

transmitter substance. They are produced in the terminal buttons by the Golgi

apparatus. The Golgi apparatus operates as a recycling center. It makes new

synaptic vesicles out of the membranes of old vesicles which have since

released their substance into the synaptic cleft. Large synaptic vesicles are

produced in the soma where they are subsequently transported down to the

terminal buttons. The large vesicles contain one of a number of differentneuropeptides.

When an action potential reaches the terminal buttons, small synaptic vesicles

located just inside the postsynaptic membrane attach themselves to the

membrane and then break open; their contents are expelled into the synaptic

cleft. The event takes only a few milliseconds. The way in which an action

potential causes synaptic vesicles to release their transmitter substance is as

follows: Some of the synaptic vesicles are docked against the presynaptic

membrane where they are ready to release their contents into the synaptic

cleft. Voltage-dependent calcium channels are located at the release zone of

the presynaptic membrane. Depolarization by an action potential causes the

calcium channels to open. At this moment, calcium ions flows into the cell

propelled by electrostatic pressure and the force of diffusion. The entering

calcium causes the fusion pore to open. While this is occurring the membrane

of the synaptic vesicle fuses with the presynaptic membrane. This causes the

vesicle to be "pulled apart" causing the release of the vesicle's neurotransmitter

into the synaptic cleft.

After the synaptic vesicle has released its payload, the terminal button gains

the vesicle's membranes that have fused with it causing the terminal to become

larger. In order for the terminal button membrane to maintain its optimum size

and cease its expansion, the newly acquired vesicle membrane is received by

the Golgi apparatus where it is recycled in the production of new synaptic

vesicles. The new vesicles are packaged with molecules of transmitter

substance and transported to the presynaptic membrane.

The neurotransmitters released by the synaptic vesicles diffuse across the


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synaptic cleft and attach to the "lock and key" binding sites of special protein

molecules attached to the postsynaptic membrane. When binding takes place,

the postsynaptic receptors open up one or more neurotransmitter-dependent

ion channels that permit the passage of specific ions into or out of the cell.

Presence of transmitter substance in the synaptic cleft allows certain ions to

pass through the membrane which the local membrane potential. The openingof ion channels by neurotransmitters can take place in one of two ways: direct

or indirect. The direct method involves the presence of the appropriate

transmitter molecular in the synaptic cleft, and a neurotransmitter-dependent

ion channel equipped with its own binding site on the postsynaptic membrane.

The postsynaptic receptor/ion channel is called an ionotropic receptor. When

a molecule of neurotransmitter attaches to the binding site it causes the ion

channel to open allowing sodium ions to enter the cell.

The indirect method of opening ion channels is more common and involves aseries of chemical events. Receptors involved with the indirect method are

called metabotropic receptors for they require the cell to expend energy in

opening the channels. One way in which ion channels are opened via the

indirect method involves the binding of the transmitter substance with the

receptor which then causes activates a G protein located nearby. The inactive

G protein contains three subunits. When activated the alpha subunit breaks

away from the other subunits and attaches to a special binding site of an ion

channel. This causes the ion channel to open permitting ions to pass through

the channel causing a postsynaptic potential.

The second method mimics the first indirect method in the first two steps, but

instead of the alpha subunit binding directly with an ion channel, it attaches to

and activates an enzyme located in the membrane. The enzyme then causes

the production of one of several different chemical in the cytoplasm of the

cell. The newly produced chemicals, called second messengers, initiate

another series of chemical steps that causes the ion channel to open resulting

in a postsynaptic potential.

Postsynaptic potentials can be either depolarizing, excitatory , or

hyperpolarizing, inhibitory. Therefore, alterations in membrane permeability

must be caused by the movement of particular types of ions. Within the

postsynaptic membrane there are four types of neurotransmitter-dependent ion

channels: sodium (Na+), potassium (K+), chloride (Cl-), and calcium (Ca2+

).

The most important source of excitatory (depolarizing) postsynaptic potentials

is the neurotransmitter-dependent sodium channel. Sodium is kept outside the

cell by sodium-potassium transporters which wait for the forces of diffusion

and electrostatic pressure to push it in. When sodium channels are openeddepolarization occurs; an excitatory postsynaptic potential takes place. The


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sodium-potassium transporters also maintain a small surplus of potassium ions

within the cell. When potassium channels are opened, some of these cations

will leave the cell. The efflux of positively charged potassium ions

hyperpolarizes the membrane generating an inhibitory postsynaptic potential.

Inhibitory transmitter substances open chloride channels at many synapses

rather than, or in addition to, potassium channels. The effect of opening

chloride channels is dependent upon the membrane potential of the neuron. If

in rest, nothing will happen because the forces of diffusion and electrostatic

pressure are perfectly balanced for the chloride ion. But, if the membrane

potential has already been depolarized by the activity of nearby excitatory

synapses the opening of chloride channels will permit chloride to leave the cell

bringing the membrane potential back to rest. Opening of chloride channels

operate in neutralizing excitatory postsynaptic potentials.

Calcium ions are positively charged ions located in high concentrations

outside the cell. When calcium channels are opened the membrane is

depolarized causing an excitatory postsynaptic potential. Certain enzymes are

activated by the release of the calcium. They have a variety of effects; such as

the production of biochemical and structural changes in the postsynaptic

neuron.

Part Three: The Major Neurotransmitters (mode of action/s):

Although neurotransmitters have two types of effects, depolarization or

hyperpolarization, many of them are not hard-wired. Many transmitters do not

always have the same effect. The nature of the ion channels that are controlled

by the postsynaptic can determine the effects of some transmitters.

Transmitter substances are generally categorized into four groups:

acetylcholine, monoamines, aminoacids , andpeptides.

A. Acetylcholine (ACh):

ACh is released at synapses on skeletal muscles and can also be found in the

ganglia of the autonomic nervous system, as well as the target organs of the

parasympathetic nervous system. Because the substance is located in

"convenient" places, outside the central nervous system, it has been

extensively studied by neuroscientists. On the membrane of skeletal muscle

fibers ACh has an excitatory effect; it exhibits an inhibitory effect upon themembrane muscle fibers in the heart. This means that effect that a transmitter


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substance has is not determined by the chemical itself, but by the nature of the

postsynaptic receptors it stimulates.

Acetylcholine is found in the brain as well. There, it is involved with learningand recall, as well as in controlling the stage of sleep during which dreams

occur. The substance is composed ofcholine and acetate; two substances

which require internal bioengineering for use as ACh. ACh is deactivated by

the enzyme acetylcholinesterase (AChE). This enzyme is present in the

postsynaptic membrane and cytoplasm of the terminal buttons.

Two types of ACh receptors exist, ionotropic and metabotropic. ACh

ionotropic receptors are stimulated by nicotine and are referred to as nicotinic

receptors. Such receptors are exclusively found in muscle fibers; smalleramounts of this receptor are found in the central nervous system.

Metabotropic ACh receptors are stimulated by muscarine, a poison found in

mushrooms, and are hence referred to as muscarinic receptors. These

receptors are primarily found in the central nervous system.

The reason that several types of receptors exist for the same neurotransmitter

substance has to do with the receptor's coupling to different kinds of ion

channels, and to different G proteins which have different physiological

effects. Ionotropic receptors produce rapid postsynaptic potentials;

metabotropic receptors produce slower and longer potentials, and can also

produce physiological processes within the cell to occur. Additionally, some

receptors are sensitive to neuromodulators causing a single neurotransmitter to

have a variety of effects in different locations of the nervous system.

B. Monoamines:

The monoamines include the four chemicals: epinephrine, norepinephrine,dopamine , and serotonin. The molecular structures of these chemicals are

similar to each other causing some drugs to affect the activity of all of them at

the same time. Epinephrine, norepinephrine, and dopamine belong to the

subclass of monoamines called catecholamines. Serotonin belongs to the

monoamines subclass called indolamines.

Monoamines are produced by several systems of neurons within the brain.

The majority of these systems consist of a small number of cell bodies located

in the back of the brain. The axons of these cells branch repeatedly giving riseto an enormous number of terminal buttons widely distributed throughout the


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brain. Monoaminergic neurons serve to modulate the function of widespread

regions throughout the brain. They serve as volume controls that increase or

decrease the activities of particular brain functions.

Dopamine (DA): Dopamine produces both excitatory and inhibitory

postsynaptic potentials depending upon the receptor site. Dopamine has been

discovered to perform various important functions associated with movement,

attention, and learning. Tyrosine is the precursor molecule for both dopamine

and norepinephrine. When tyrosine receives OH it becomes l-DOPA. The

enzyme DOPA decarboxylase causes the l-DOPA to lose a carboxyl group

causing it to become dopamine. When the enzyme beta-hydroxylase attaches

a hydroxyl group to dopamine it creates norepinephrine. The enzyme

monoamine oxidase (MAO) regulates the production of the catecholamines.

MAO is found in the blood where it deactivates amines which could

potentially cause dangerous increases in blood pressure.

Parkinson's disease is caused by the degeneration of dopaminergic neurons

which serve to connect two parts of the brain's motor system. This disease is

characterized by tremors, rigidity of the limbs, poor balance, and difficulty in

initiating movements. The cell bodies of these neurons are located in the

brain's substantia nigra. Those with Parkinson's disease are given l-DOPA

which serves to stimulate the production of dopamine. Consequently, a

patient's symptoms can be alleviated.

Dopamine may also prove to have a connection with the mental disorder

schizophrenia. The disorder involves hallucinations, delusions, and the

disruption of normal, logical thought processes. Drugs which block activity of

dopaminergic neurons reduce these symptoms causing researchers to speculate

that schizophrenia is caused by overactivity of these neurons. Furthermore,

patients with Parkinson's disease being treated with l-DOPA occasionally

display schizophrenic symptoms.

There are at least five types of dopamine receptors, all of which are

metabotropic. The two most important ones are theD1 andD2 dopamine

receptors. The D1 receptors appear to be exclusively postsynaptic.

Stimulation of these receptors increases the production of the second

messenger cyclic AMP. D2 receptors are found both presynaptically and

postsynaptically in the brain; stimulation of the D2 receptors casuses a

decrease in AMP.


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Most of the neurons that release catecholamines do so through axonal

varicosities, beadlike swellings of the axonal branches. The varicosities give

the axonal branches the appearance of beaded chains. They form synapses

with the base of the dendritic spines or the dendritic shaft.

Epinephrine / Norepinephrine (NE): Like ACh, norepinephrine is also found

in the autonomic nervous system and has been subjected to extensive

research. The chemicals are also referred to as Adrenalin and noradrenalin.

Epinephrine is a hormone that is produced by the adrenal medulla. It has also

been discovered that epinephrine serves as a transmitter substance in the brain;

yet it is not as important as norepinephrine. The transmitter substance is

referred to as norepinephrine, whereas its adjectival form is noradrenergic.

Noradrenergic neurons within the brain are involved with the control of

alertness and wakefulness. Their synapses in the central nervous system

produce inhibitory postsynaptic potentials. At the target organs of the

sympathetic nervous system they typically have an excitatory effect. The

transmitter is produced from dopamine with its final step of synthesis

occurring inside synaptic vesicles. Once the vesicles are filled with dopamine,

the dopamine is converted to norepinephrine through the action of dopamine

beta-hydroxylase. Monoamine oxidase destroys excessive amounts of

norepinephrine in the terminal buttons.

Several types of noradrenergic receptors exist. The receptors are usually

called adrenergic receptors for they are sensitive to epinephrine and

norepinephrine. Neurons in the central nervous system contain bothB1 and

B2 adrenergic receptors and alpha1 and alpha2 adrenergic receptors. These

four types of receptors are also found in various organs where they are

responsible for the effects of the catecholamines when they function as

hormones. All four receptors are also coupled to G proteins that generate

AMP.

Serotonin (5-HT): Serotonin produces inhibitory postsynaptic potentials at

most synapses. Most of its behavioral effects are also inhibitory. 5-HT is

known to play a role in the regulation of mood; the control of eating; the

control of sleep and arousal; and in the regulation of pain. The serotonergic

neurons are involved with the control of dreaming. LSD hallucinations appear

to be caused by the drug interfering with the activity of serotonergic synapses

which causes the user to dream while he/she is awake. The amino acid

tryptophan is the precursor for serotonin. The enzyme tryptophan hydroxylase

adds a hydroxyl group which produces 5-HTP. The enzyme 5-HTPdecarboxylase removes a carboxyl group from 5-HTP resulting in 5-HT,


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serotonin. Seven types of serotonin receptors have been discovered. Of the

seven 5-HT2 receptors are found exclusively in postsynaptic membranes. The

other six have been found presynaptically and postsynaptically. With the

exception of the 5-HT3 receptor, all serotonin receptors are metabotropic.

C. Amino Acids:

Glutamic Acid (glutamate): Glutamic acid and GABA produce postsynaptic

potentials by activating postsynaptic receptors. Glutamic acid has direct

excitatory effects on axons; GABA has inhibitory effects. The two substances

serve to raise and lower the threshold of excitation which affects the rate at

which action potentials occur. Glutamate is found throughout the brain where

it appear to be the principal excitatory transmitter substance. MSG, as found

in some Oriental food, contains the sodium salt of glutamic acid that can cause

the mild neurological symptoms of dizziness and numbness in some people.Five types of Glutamic receptors have been found. Three are ionotropic, the

other two metabotropic. The NMDA receptor has been linked to producing

some of the synaptic changes responsible for learning.

Gamma-aminobutyric Acid (GABA): GABA is produced from glutamic acid

through action of the enzyme GAD which removes a carboxyl group. GABA

is an inhibitory transmitter substance with widespread distribution throughout

the brain and spinal cord. The GABAA

receptor is ionotropic and controls a

chloride channel. The GABAB receptor is metabotropic and controls a

potassium channel. GABA-secreting neurons normally produce an inhibitory

influence and are present in large numbers throughout the brain. Some

research suggests that epilepsy is caused by an abnormality in the

biochemistry of GABA-secreting neurons.

GABAA receptors contain binding sites for at least three transmitter substances

and neuromodulators. The main site is for GAGA, whereas a second site

binds with a class of tranquilizing drugs known as the benzodiazepines, whichincludes Valium and Librium. These drugs reduce anxiety, promote sleep,

reduce seizure activity, and produce muscle relaxation. The third site binds to

barbiturates and alcohol. Because GABA is an inhibitory neurotransmitter, the

effects of benzodiazepines, barbiturates, and alcohol are the increase of neural

inhibition. It is believed that the presence of these receptor sites implies that

the brain produces neuromodulators that cause a stress reaction by either

blocking or activating these receptors.

Glycine: This amino acid is thought to be the inhibitory neurotransmitter inthe spinal cord and lower portions of the brain. Although more research is


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needed to better understand glycine, it is known that the bacteria that cause

tetanus release a chemical that blocks the activity of glycine synapses. The

removal of the inhibitory effect of these synapses causes the muscles to

contract continuously.

D. Peptides:

Peptides consist of two or more amino acids that are linked together by peptide

bonds. They are synthesized by the ribosomes according to the instructions

contained on the chromosomes of the nucleus. Neurons release several

different peptides; most acting as neuromodulators, while some serve as

neurotransmitters. The endogenous opioids comprise one of the most

important families of peptides. These are the brain's natural opiates which

help to reduce pain. Three different types of opioid receptors have been

detected.

When opiate receptors are stimulated several different neural systems are

activated. One system produces analgesia, another inhibits species-typical

defensive responses, while another stimulates a system of neurons involved

with internal reward/ reinforcement. Stimulation of the body's internal reward

system helps explain why opiates are abused.

Released peptides are deactivated by enzymes and are not returned to the

terminal buttons and recycled. The releasement of peptides is done in

combination with one of the "classical" neurotransmitters. The reason for this

is that peptides can regulate the sensitivity of presynaptic or postsynaptic

receptors to the neurotransmitter. For example, the terminal buttons of the

salivary nerve in a cat release both ACh and the peptide VIP. Only ACh is

released while the axon fires at a low rate. This causes mild secretion of

saliva. When the axon fires at a higher rate, both ACh and VIP are released.

The additional presence of VIP causes a dramatic in increase in the sensitivity

of the muscarinic receptors in the salivary gland to ACh which causes muchmore saliva to be released.

Peptide hormones are also found in the brain where they serve as either

neurotransmitters or neuromodulators. Sometimes the peripheral and the

central peptide perform related functions. Example: Outside the nervous

system the hormone angiotensin acts directly on the kidneys and blood vessels

helping them cope with the loss of fluid, and inside the nervous system circuits

of neurons that use angiotensin as a neurotransmitter perform similar

functions.


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Part Four: The Limbic System (components + functions).

In 1937 neuroanatomist Papez discovered a set of interconnected brain

structures that formed a circuit which functioned as the brain's center for

motivation and emotion. The system appeared to consist of a set of

interconnected structures surrounding the core of the forebrain. Parts of the

limbic cortex, another form of the cerebral cortex located around the edge of

the cerebral hemispheres, were also included in Papez's system. The system

was later expanded by Paul MacLean in 1949 to include additional structures;

it became known as the limbic system in 1952. The limbic system is the seat

of emotion, and is associated with learning and memory. In addition to

regions of the limbic cortex, the primary structures of the limbic system are

hippocampus and amygdala. The cingulate gyrus is also associated with the

limbic system.

Originally associated with emotion, it was later discovered that the

hippocampal formation and the regions of the limbic cortex that surround it

function in the processes of learning and memory. Today, it is clear that the

limbic is directly involved with emotion, and plays a role in learning and

memory.

Early experiments on the limbic system demonstrated that specific limbic sites

triggered emotion. Electrical stimulation of one region produced sudden

anger, another rage, yet another, joy. However, while the site of emotion was

discovered, the structures of the site were revealed not to be hard-wired.

Stimulation of the amygdala would produce fear one day; elation the next. In

time it was discovered that both the hippocampus and amygdala plays a role in

memory. The hippocampus is known to consolidate and store memory, and

the amygdala is believed to have perceptual and memory functions.

In addition to coining the term limbic system, MacLean has also developed the

triune brain theory. While studying the evolution of the limbic system,

MacLean discovered that its evolutionary appearance is marked by the initial

appearance of the cerebral cortex, and the development of emotional

responses. The triune brain theory looks at the evolutionary stages of the brain

and postulates that the human brain is actually three brains in one. The three

brains of MacLean's triune brain theory are: the reptilian brain, the mammalian

brain, and the "human" brain.


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The reptilian brain includes the brain stem and its primary functions of

keeping the organism alive. The mammalian brain resides in the limbic

system. Its primary purpose is survival and preservation of self and species.

Behavior of the mammalian brain is said to revolve around feeding, fighting,fleeing, and mating. For the mammalian brain there are no neutral emotions;

all emotions are either agreeable or disagreeable. Through the mammalian

brain mammals, including humans, feel pleasure when engaged in activities

that enhance their preservation or the preservation of their species. Pain is

experienced when survival needs are thwarted. From the limbic system's

perspective all experiences are judged in the dualistic fashion of pain or

pleasure. The limbic brain scans for differences; typically when one is found it

is deemed a threat to survival. The cerebral cortex comprises the "human"

brain and is associated with advanced functions such as planning, thinking,

analyzing, and communicating.

The limbic brain can be seen as receiving its cues from the inside. Whereas

the neocortex processes sensory information from the external world, the

limbic system has, according to MacLean, a loose grip on reality. Temporal

lobe epilepsy, resulting in limbic storms, produces the overwhelming feeling

of experiencing truth. Without the reality check of the neocortex, the limbic

system is capable of producing sensations of deja-vu, sudden memories,

waking dreams, messages from God, even religious conversions.

Cingulate Gyrus:

MacLean states that the cingulate gyrus involves three distinct behaviors:

nursing and maternal care, play, and audio-vocal communication. The three

behaviors are exhibited my mammals which have a cingulate gyrus, and not by

reptiles who lack a cingulate gyrus. The cortex covering the cingulate gyrus is

an important part of the limbic system. Research indicates that it provides aninterface between the decision-making processes of the frontal cortex, the

emotional functions of the limbic system, and the brain mechanisms

controlling movement. The cingulate gyrus communicates with the rest of the

limbic system and other regions of the frontal cortex. Electrical stimulation of

this part of the limbic system produces feelings that are either emotionally

positive or negative. In general, the cingulate gyrus plays an excitatory role in

emotions and motivated behavior.

Hippocampus:


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The hippocampus is comprised of rows of 40 million nerve cells. If the

hippocampus or pathways to it are damaged the ability to make new memories

disappears; its function is to work on converting short-term memory into long-

term memory. The hippocampus is considered important for localization

memory. Interestingly, subtle clues into the physiological aspects of

schizophrenia have been linked to the hippocampus. While still controversial,evidence has been found showing that the cells of the hippocampus which are

normally arranged in an ordered manner, are grossly misaligned in the brains

of schizophrenics. Such cells were seen to be rotated ninety degrees and some

had their dendrites upside down. Cellular disarray of the hippocampus as seen

in schizophrenics is believed to be genetic, or the consequence of a viral

infection in the womb.

The hippocampus in the right hemisphere of the brain is concerned with

visual, emotional, tactile, and nonverbal memories. The hippocampus in theleft hemisphere stores verbal and mathematical memories. Ultimately, the

hippocampus stores in memories that are of emotional and motivational

significance.

Amygdala:

The job of the amygdala is to discern the emotional significance of all aspects

of experience. It adds color to thoughts and is responsible for the capacity to

feel complex emotions like love and anxiety. The amygdala is extremely

sensitive to tactile stimulation and is involved with memory. This limbic

structure is interconnected with the hypothalamus, septal nucleus, and

hippocampus.

Visual and auditory perceptual information is received by the amygdala

causing an emotional influence on our perception and thought. Damage to the

amygdala can cause a person to misperceive or fail to perceive societal cues

which are emotionally based. Traditionally, the amygdala has been linked toviolent tendencies and behavior. This association dates back to 1968 when

three prison inmates had parts of their amygdala burned out with electrodes to

exorcise their violent nature. the basis for this was founded upon research that

showed amygdalectomy being capable of taming vicious animals. Its success

with the inmates was insignificant.

Other Structures of the Limbic System:

Hypothalamus: The hypothalamus controls and monitors hunger, thirst, andthe ability to feel extreme pain or pleasure. Being the most primitive part of


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the limbic system, the hypothalamus it is the source from which all emotions

originate as raw, powerful, undirected feelings. This structure represents the

emotional core of our being.

The hypothalamus is also closely involved with all aspects of sexual behavior:

postures, ejaculation, and hormonal secretions relating to pregnancy and

menstrual cycles. Differences between the hypothalamus of a man and woman

indicate that the hypothalamus of females is more intricate and complex than

males. Consideration of this fact yields insight on emotional gender

differences.

The hypothalamus is capable of exerting tremendous influence over the rest of

the brain. Fortunately, it is normally controlled, in part, by the frontal lobes ofthe brain and the more recent limbic structures such as the amygdala. [also

see hypothalamusdiscussed in question #1].

Septal Nuclei: This structure is involved with humankind's ability to form

emotional and social bonds with one another. The septal nuclei also exerts

dampening effects on mood. By tapping into the emotional reservoir of the

hypothalamus, the septal nuclei is able to exert emotional influence upon the

rest of the brain. It is also interconnected with the hippocampus (thus likely to

influence memory), and in some ways it serves to counteract the amygdala.

Stimulation of the septum is known to generate strong feelings of pleasure.

Part Five: The Autonomic Nervous System:

Essentially, the nervous system is one system. However, it is divided into two

primary parts based upon their different locations. The parts of the nervous

system within the brain and spinal cord are considered the central nervous

system. The parts of the nervous system extending outside the brain and

spinal cord are classified together as the peripheral nervous system. With this

distinction in mind, the peripheral nervous system serves as a network of

nerves that allows the brain and spinal cord to interact and communicate with

parts of the body existing outside the central nervous system.


23/27

Further distinction results in a peripheral nervous system that is broken down

into two primary parts: the somatic nervous system and the autonomic nervous

system. The somatic nervous system involves the part of the peripheral

nervous system which receives sensory information from the sense organs andcontrols movement of the skeletal muscles. The autonomic nervous system is

involved with the self-governing (automatic) regulation of three aspects of the

body: smooth muscle, cardiac muscle, and the glands.

Smooth muscle is found in various places throughout the body and is regulated

by the autonomic nervous system. It can be found in the skin where it enables

hair to assist in bodily temperature regulation. Smooth muscle controls the

eye's pupil size and accommodates the lens. The gall bladder, urinary bladder,

blood vessels, and walls and sphincters of the gut contain smooth muscle. Theautonomic nervous system controls the actions of the glands. It controls the

functions and involuntary muscles of the respiratory, circulatory, digestive,

and urogenital systems.

The autonomic nervous system regulates these parts of the body by sending

impulses to them. The impulses are controlled by nerve centers in the lower

part of the brain. Furthermore, the autonomic nervous system has a reciprocal

effect on the internal secretions. The system is influenced by hormones to a

certain degree, and it reciprocates this by influencing the rate of hormone

production. In this respect the purpose of the autonomic nervous system

involves the automatic regulation of "vegetative processes" in the

body.

Two antagonistic and anatomically separate systems comprise the autonomic

nervous system. The two systems are called the sympathetic and

arasympathetic divisions. With few exceptions, the two subdivisions

influence and act upon the organs of the body; each system having a differenteffect.

The Sympathetic Division:

The sympathetic division of the autonomic nervous system stimulates the

heart, dilates the bronchi, contracts the arteries, and inhibits the digestive

system during moments of danger. This system serves to prepare the organism

for fighting in order to help ensure survival in face of an environmental threat.

The effect of the sympathetic division deals with the rapid accumulation andconcentration of energy reserves stored in the body which can be utilized and


24/27

directed toward ensuring survival. Rather than having energy being expended

upon digestion while the immediate survivability of the organism is

threatened, the sympathetic division harnesses such energy reserves in

preparing the body for fight or flight.

In addition to other physiological changes, when the sympathetic division is

activated blood flow to the skeletal muscles is increased, the secretion of

epinephrine is stimulated causing the heart rate and blood sugar level to rise,

and piloerection occurs.

The sympathetic division is widely distributed throughout the body. It arises

from the middle portion of the spinal cord, joins the sympathetic ganglionated

chain (sympathetic preventebral ganglia), and courses throughout the spinalnerves. This system of nerves connects the sympathetic division to the eyes,

salivary gland, sweat glands and blood vessels in the skin, heart, lungs,

stomach, kidneys and adrenals, pancreas, intestines, external genitalia, and

bladder.

Motor neurons of the sympathetic division are located in the gray matter of the

thoracic and lumbar regions of the spinal cord. For this reason the sympathetic

nervous system is also called the thoracicolumbarsystem. The fibers of these

neurons exit the ventral roots and, once joined with the spinal nerves, branch

off and pass into spinal sympathetic ganglia. Axons leaving the spinal cord

through the ventral root form part of thepreganglionic neurons. With the

exception of the medulla adrenal, all sympathetic preganglionic axons enter

the ganglia of the sympathetic chain, though not all of them synapse there.

Some of the axons connect to other sympathetic ganglia located among the

internal organs. Synaptic connection occurs in one of the ganglia.

Postganglionic neurons are nerves which have formed a synapse with

preganglionic axons inside one of the ganglia. These neurons send axons to

one of the target organs of the sympathetic nervous system.

Also under control of the sympathetic nervous system is the adrenal medulla,

a cluster of cells located in the center of the adrenal gland. Closely resembling

a sympathetic ganglion, the adrenal medulla is infused with preganglionic

sympathetic neurons. The secretory cells of the adrenal medulla are similar to

postganglionic sympathetic neurons. When stimulated the cells secrete

epinephrine and norepinephrine which aid sympathetic functioning.


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The Parasympathetic Division:

The parasympathetic nervous system arises above and below the sympathetic

nervous system from the brain and from the lower part of the spinal cord. The

parasympathetic division produces the opposite effect of the sympathetic

division. Whereas the sympathetic division prepares the organism foroptimum fight/flight functioning, the parasympathetic division prepares the

organism for feeding, digestion, and rest. The parasympathetic division

supports activities which assist in increasing the body's supply of energy.

Activities include: salvation, gastric and intestinal motility, secretion of

digestive juices, and increased blood flow to the gastrointestinal system.

Cell bodies giving rise to preganglionic axons in the parasympathetic division

are found in two areas: the nuclei of some of the cranial nerves; and, the

intermediate horn of the gray matter in the sacral region of the spine. Becauseof this the parasympathetic division is sometimes called the craniosacral

system. Ganglia of the parasympathetic division are located close to the target

organs. This makes postganglionic parasympathetic relatively short. The

terminal buttons of both pre and postganglionic neurons in the

parasympathetic division secrete acetylcholine. With the exception of the

adrenal medulla, the parasympathetic division has connections with the same

organs as the sympathetic nervous system.

Part Six: The Reticular Formation (function and location):

The reticular formation is composed of more than 90 nuclei located in the core

of the medulla, pons, and midbrain; the three major of the brain stem. It has

an intriguing netlike appearance (reticulum means little net) of diffuse neurons

with complex dendritic and axonal processes. This network of cells, the

reticular formation, is distributed along the length of a cerebrospinal fluidcanal that runs longitudinally through the brain stem.

The reticular formation receives sensory information through various

pathways and has axonal connections to the cerebral cortex, thalamus, and

spinal cord.

The reticular formation functions as the brain's on/off switch. It is likened to

an all-important sentinel that keeps the brain "awake" even during sleep.

Damage to the reticular formation can result in a coma. The formation alsoregulates muscle tonus by controlling the activity of the gamma motor system.


26/27

In addition to these two functions the reticular formation also plays in a role in

motor activity, the transition between sleep and wakefulness, and alertness.

The pons are another part of the reticular formation serving as the controls fordreaming and waking. In the 1950's French physiologist Michel Jouvet was

able to prove that the pons controlled REM sleep, and that another part of the

reticular formation produces dreamless, non-REM sleep. One of the

subregions of the pons, called the locus coeruleus, sends axons to the cortex.

It has been discovered that when something interesting or threatening happens

to an animal, the cells of the locus coeruleus fire excitedly- this could serve to

instruct the brain to be alert and pay attention.

Part of the reticular formation is also found in the medulla oblongata whichcontrols vital bodily functions, including reflex activities such vomiting.

Furthermore, ventromedial pathways originating in the superior colliculi,

vestibular nuclei, and reticular formation indicates that the reticular formation

plays a role in the control of posture. Other evidence indicates that the

reticular formation plays a part in locomotion.

Understanding of the reticular formation is far from complete. New research

shows the reticular formation playing roles in a variety of physiological

functions. In 1977 research on cats showed that specific bodily movement

generated responses in certain neurons located in the reticular formation. This

research may suggest that the reticular formation plays an important role in

controlling movements. However, the function of these specific neurons and

the range of motion they control is unknown.

BIBLIOGRAPHY

"Autonomic Nervous System," Microsoft (R) Encarta. Copyright (c) 1994

Microsoft Corporation. Copyright (c) 1994 Funk & Wagnall's Corporation.

"Brain," Microsoft (R) Encarta. Copyright (c) 1994 Microsoft Corporation.


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Copyright (c) 1994 Funk & Wagnall's Corporation.

Carlson, N. (1977). Physiology of Behavior, 5th

ed. Boston, MA: Allyn and

Bacon.

Hooper, J. & Teresi, D. The 3-Pound Universe. New York: G.P. Putnam'sSons.

Joseph, R., Dr. The Right Brain and the Unconscious: Discovering the

Stranger Within. New York: Plenum Press.

"Nervous System," Microsoft (R) Encarta. Copyright (c) 1994 Microsoft

Corporation. Copyright (c) 1994 Funk & Wagnall's Corporation.

"Neurophysiology," Microsoft (R) Encarta. Copyright (c) 1994 Microsoft

Corporation. Copyright (c) 1994 Funk & Wagnall's Corporation.

Copyright 1998, EnSpire Press, EnSpire Audio, EnSpire Publishing. All rights

reserved.

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