Description

In this collection, we will go over The Nervous System talking about the General functions of the CNS, Generation and propagation of an action potential, The Peripheral Nervous System, The Sympathetic and Parasympathetic Systems, Nervous Tissue, The Limbic System and Higher Mental Functions.

This collection is important to all medical students

Study Set Content:
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Human Physiology/The Nervous System

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Human Physiology/The Nervous System

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Integumentary System 

 

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Answers

The 

central nervous system 

includes the 

brain 

and 

spinal cord

. The brain and spinal cord are protected by bony

structures, membranes, and fluid. The brain is held in the cranial cavity of the skull and it consists of the 

cerebrum

,

cerebellum

, and the 

brain stem

. The nerves involved are cranial nerves and spinal nerves.

Nervous system

Overview of the entire nervous system

The nervous system has three main functions: sensory input,

integration of data and motor output. Sensory input is when the body

gathers information or data, by way of neurons, glia and synapses. The

nervous system is composed of excitable nerve cells (neurons) and

synapses that form between the neurons and connect them to centers

throughout the body or to other neurons. These neurons operate on

excitation or inhibition, and although nerve cells can vary in size and

location, their communication with one another determines their

function. These nerves conduct impulses from sensory receptors to the

brain and spinal cord. The data is then processed by way of integration

of data, which occurs only in the brain. After the brain has processed

the information, impulses are then conducted from the brain and spinal

cord to muscles and glands, which is called motor output. Glia cells are

found within tissues and are not excitable but help with myelination,

ionic regulation and extracellular fluid.

The nervous system is comprised of two major parts, or subdivisions,

the central nervous system (CNS) and the peripheral nervous system

(PNS). The CNS includes the brain and spinal cord. The brain is the

body's "control center". The CNS has various centers located within it

that carry out the sensory, motor and integration of data. These centers can be subdivided to Lower Centers

(including the spinal cord and brain stem) and Higher centers communicating with the brain via effectors. The PNS

is a vast network of spinal and cranial nerves that are linked to the brain and the spinal cord. It contains sensory

receptors which help in processing changes in the internal and external environment. This information is sent to the

CNS via afferent sensory nerves. The PNS is then subdivided into the autonomic nervous system and the somatic

nervous system. The autonomic has involuntary control of internal organs, blood vessels, smooth and cardiac

muscles. The somatic has voluntary control of skin, bones, joints, and skeletal muscle. The two systems function

together, by way of nerves from the PNS entering and becoming part of the CNS, and vice versa.

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General functions of the CNS

Brain, brain stem, and spinal chord.

CNS:

The "Central Nervous System", comprised of brain, brainstem, and

spinal cord.

The central nervous system (CNS) represents the largest part of the

nervous system, including the brain and the spinal cord. Together, with

the peripheral nervous system (PNS), it has a fundamental role in the

control of behavior.

The CNS is conceived as a system devoted to information processing,

where an appropriate motor output is computed as a response to a

sensory input. Many threads of research suggest that motor activity

exists well before the maturation of the sensory systems, and senses

only influence behavior without dictating it. This has brought the

conception of the CNS as an autonomous system.

Structure and function of neurons

Structure

Neurons are highly specialized for the processing and transmission of

cellular signals. Given the diversity of functions performed by neurons in different parts of the nervous system, there

is, as expected, a wide variety in the shape, size, and electrochemical properties of neurons. For instance, the soma of

a neuron can vary in size from 4 to 100 micrometers in diameter.

The soma (cell body) is the central part of the neuron. It contains the nucleus of the cell, and therefore is where most

protein synthesis occurs. The nucleus ranges from 3 to 18 micrometers in diameter. The dendrites of a neuron are

cellular extensions with many branches, and metaphorically this overall shape and structure is referred to as a

dendritic tree. This is where the majority of input to the neuron occurs. However, information outflow (i.e. from

dendrites to other neurons) can also occur (except in chemical synapse in which backflow of impulse is inhibited by

the fact that axon do not possess chemoreceptors and dendrites cannot secrete neurotransmitter chemical). This

explains one way conduction of nerve impulse. The axon is a finer, cable-like projection which can extend tens,

hundreds, or even tens of thousands of times the diameter of the soma in length. The axon carries nerve signals away

from the soma (and also carry some types of information back to it). Many neurons have only one axon, but this

axon may - and usually will - undergo extensive branching, enabling communication with many target cells. The part

of the axon where it emerges from the soma is called the 'axon hillock'. Besides being an anatomical structure, the

axon hillock is also the part of the neuron that has the greatest density of voltage-dependent sodium channels. This

makes it the most easily-excited part of the neuron and the spike initiation zone for the axon: in neurological terms it

has the greatest hyperpolarized action potential threshold. While the axon and axon hillock are generally involved in

information outflow, this region can also receive input from other neurons as well. The axon terminal is a specialized

structure at the end of the axon that is used to release neurotransmitter chemicals and communicate with target

neurons. Although the canonical view of the neuron attributes dedicated functions to its various anatomical

components, dendrites and axons often act in ways contrary to their so-called main function.

Axons and dendrites in the central nervous system are typically only about a micrometer thick, while some in the 

peripheral nervous system are much thicker. The soma is usually about 10

25 micrometers in diameter and often is 

not much larger than the cell nucleus it contains. The longest axon of a human motor neuron can be over a meter 

long, reaching from the base of the spine to the toes. Sensory neurons have axons that run from the toes to the dorsal 

columns, over 1.5 meters in adults. Giraffes have single axons several meters in length running along the entire

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length of their necks. Much of what is known about axonal function comes from studying the squids giant axon, an

ideal experimental preparation because of its relatively immense size (0.5

1 millimeters thick, several centimeters

long).

Function

Sensory afferent neurons convey information from tissues and organs into the central nervous system. Efferent

neurons transmit signals from the central nervous system to the effector cells and are sometimes called motor

neurons. Interneurons connect neurons within specific regions of the central nervous system. Afferent and efferent

can also refer generally to neurons which, respectively, bring information to or send information from brain region.

Classification by action on other neurons

Excitatory neurons excite their target postsynaptic neurons or target cells causing it to function. Motor neurons and

somatic neurons are all excitatory neurons. Excitatory neurons in the brain are often glutamatergic. Spinal motor

neurons, which synapse on muscle cells, use acetylcholine as their neurotransmitter. Inhibitory neurons inhibit their

target neurons. Inhibitory neurons are also known as short axon neurons, interneurons or microneurons. The output

of some brain structures (neostriatum, globus pallidus, cerebellum) are inhibitory. The primary inhibitory

neurotransmitters are GABA and glycine. Modulatory neurons evoke more complex effects termed

neuromodulation. These neurons use such neurotransmitters as dopamine, acetylcholine, serotonin and others. Each

synapses can receive both excitatory and inhibitory signals and the outcome is determined by the adding up of

summation.

Excitatory and inhibitory process

Nerve Synapse

The release of a excitatory neurotransmitter

(ACHe) at the synapses will cause an inflow

of positively charged sodium ions (Na+)

making a localized depolarization of the

membrane. The current then flows to the

resting (polarized) segment of the axon.

Inhibitory synapse causes an inflow of Cl-

(chlorine) or outflow of K+ (potassium)

making the synaptic membrane

hyperpolarized. This increase prevents

depolarization, causing a decrease in the

possibility of an axon discharge. If they are

both equal to their charges, then the

operation will cancel itself out. There are

two types of summation: spatial and temporal. Spatial summation requires several excitatory synapses (firing several

times) to add up,thus causing an axon discharge. It also occurs within inhibitory synapses, where just the opposite

will occur. In temporal summation, it causes an increase of the frequency at the same synapses until it is large

enough to cause a discharge. Spatial and temporal summation can occur at the same time as well.

The neurons of the brain release inhibitory neurotransmitters far more than excitatory neurotransmitters, which helps

explain why we are not aware of all memories and all sensory stimuli simultaneously. The majority of information

stored in the brain is inhibited most of the time.

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Summation

When excitatory synapses exceed the amount of inhibitory synapses there are, then the excitatory synapses will

prevail over the other. The same goes with inhibitory synapses, if there are more inhibitory synapses than excitatory,

the synapses will be inhibited. To determine all of this is called summation.

Classification by discharge patterns:

Neurons can be classified according to their electrophysiological characteristics (note that a single action potential is

not enough to move a large muscle, and instead will cause a twitch).

Tonic or regular spiking: 

Some neurons are typically constantly (or tonically) active. Example: interneurons in

neurostriatum.

Phasic or bursting: 

Neurons that fire in bursts are called phasic.

Fast spiking: 

Some neurons are notable for their fast firing rates. For example, some types of cortical inhibitory

interneurons, cells in globus pallidus.

Thin-spike: 

Action potentials of some neurons are more narrow compared to the others. For example, interneurons

in prefrontal cortex are thin-spike neurons.

Classification by neurotransmitter released:

Some examples are cholinergic, GABAergic, glutamatergic and dopaminergic neurons.

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Central Nervous System

The central nervous system is the control center for the body. It regulates organ function, higher thought, and

movement of the body. The central nervous system consists of the brain and spinal cord.

Generation & propagation of an action potential

Electrical characteristics of a neurochemical action potential.

The Nerve Impulse

When a nerve is stimulated the resting potential changes. Examples of such stimuli are pressure, electricity,

chemicals, etc. Different neurons are sensitive to different stimuli(although most can register pain). The stimulus

causes sodium ion channels to open. The rapid change in polarity that moves along the nerve fiber is called the

"ACTION POTENTIAL." This moving change in polarity has several stages:

Depolarization

The upswing is caused when positively charged sodium ions(Na+) suddenly rush through open sodium gates

into a nerve cell.The membrane potential of the stimulated cell undergoes a localized change from-65

millivolts to 0 in a limited area. As additional sodium rushes in, the membrane potential actually reverses its

polarity so that the outside of the membrane is negative relative to the inside. During this change of polarity

the membrane actually develops a positive value for a moment(+40 millivolts). The change in voltage

stimulates the opening of additional sodium channels (called a voltage-gated ion channel). This is an example

of a positive feedback loop.

Repolarization

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(The downswing) is caused by the closing of sodium ion channels and the opening of potassium ion channels.

Release of positively charged potassium ions (K+) from the nerve cell when potassium gates open. Again,

these are opened in response to the positive voltage--they are voltage gated. This expulsion acts to restore the

localized negative membrane potential of the cell (about -65 or -70 mV is typical for nerves).

Refractory phase

is a short period of time after the depolarization stage. Shortly after the sodium gates open they close and go

into an inactive conformation. The sodium gates cannot be opened again until the membrane is repolarized to

its normal resting potential. The sodium-potassium pump returns sodium ions to the outside and potassium

ions to the inside. During the refractory phase this particular area of the nerve cell membrane cannot be

depolarized. This refractory area explains why action potentials can only move forward from the point of

stimulation.

Increased permeability of the sodium channel occurs when there is a deficit of calcium ions. when there is a deficit

of calcium ions (Ca+2) in the interstitial fluid the sodium channels are activated (opened) by very little increase of

the membrane potential above the normal resting level. The nerve fiber can therefore fire off action potentials

spontaneously, resulting in tetany. Could be caused by the lack of hormone from parathyroid glands. could be caused

by hyperventilation, which leads to a higher pH, which causes calcium to bind and become unavailable. Speed of

conduction. This area of depolarization/repolarization/recovery moves along a nerve fiber like a very fast wave. In

myelinated fibers, conduction is hundreds of times faster because the action potential only occurs at the nodes of

Ranvier (pictured below in 'types of neurons') by jumping from node to node. This is called "saltatory" conduction.

Damage to the myelin sheath by the disease can cause severe impairment of nerve cell function. Some poisons and

drugs interfere with nerve impulses by blocking sodium channels in nerves. See discussion on drug at the end of this

outline.

Brain

A color-coded image of the brain, showing the

main sections.

The brain is found in the cranial cavity. Within it are found the higher

nerve centers responsible for coordinating the sensory and motor

systems of the body (forebrain). The brain stem houses the lower nerve

centers (consisting of midbrain, pons, and medulla),

Medulla

The medulla is the control center for respiratory, cardiovascular and

digestive functions.

Pons

The pons houses the control centers for respiration and inhibitory functions. Here it will interact with the cerebellum.

Cerebrum

The cerebrum, or top portion of the brain, is divided by a deep crevice, called the longitudinal sulcus. The

longitudinal sulcus separates the cerebrum in to the right and left hemispheres. In the hemispheres you will find the

cerebral cortex, basal ganglia and the limbic system. The two hemispheres are connected by a bundle of nerve fibers

called the corpus callosum. The right hemisphere is responsible for the left side of the body while the opposite is true

of the left hemisphere. Each of the two hemispheres are divided into four separated lobes: the frontal in control of

specialized motor control, learning, planning and speech; parietal in control of somatic sensory functions; occipital in

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control of vision; and temporal lobes which consists of hearing centers and some speech. Located deep to the

temporal lobe of the cerebrum is the insula.

Cerebellum

The cerebellum is the part of the brain that is located posterior to the medulla oblongata and pons. It coordinates

skeletal muscles to produce smooth, graceful motions. The cerebellum receives information from our eyes, ears,

muscles, and joints about what position our body is currently in (proprioception). It also receives output from the

cerebral cortex about where these parts should be. After processing this information, the cerebellum sends motor

impulses from the brainstem to the skeletal muscles. The main function of the cerebellum is coordination. The

cerebellum is also responsible for balance and posture. It also assists us when we are learning a new motor skill, such

as playing a sport or musical instrument. Recent research shows that apart from motor functions cerebellum also has

some emotional role.

The Limbic System and Higher Mental Functions

Image of the brain, showing the Limbic system.

The Limbic System

The Limbic System is a complex set of structures found just beneath

the cerebrum and on both sides of the thalamus. It combines higher

mental functions, and primitive emotion, into one system. It is often

referred to as the emotional nervous system. It is not only responsible

for our emotional lives, but also our higher mental functions, such as

learning and formation of memories. The Limbic system explains why

some things seem so pleasurable to us, such as eating and why some

medical conditions are caused by mental stress, such as high blood

pressure. There are two significant structures within the limbic system

and several smaller structures that are important as well. They are:

1. The Hippocampus

2. The Amygdala

3. The Thalamus

4. The Hypothalamus

5. The Fornix and Parahippocampus

6. The Cingulate Gyrus

Structures of the Limbic System

Hippocampus

The Hippocampus is found deep in the temporal lobe, shaped like a seahorse. It consists of two horns that

curve back from the amygdala. It is situated in the brain so as to make the prefrontal area aware of our past

experiences stored in that area. The prefrontal area of the brain consults this structure to use memories to

modify our behavior. The hippocampus is responsible for memory.

Amygdala

The Amygdala is a little almond shaped structure, deep inside the anteroinferior region of the temporal lobe,

connects with the hippocampus, the septi nuclei, the prefrontal area and the medial dorsal nucleus of the

thalamus. These connections make it possible for the amygdala to play its important role on the mediation and

control of such activities and feelings as love, friendship, affection, and expression of mood. The amygdala is

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the center for identification of danger and is fundamental for self preservation. The amygdala is the nucleus

responsible for fear.

Thalamus

Lesions or stimulation of the medial, dorsal, and anterior nuclei of the thalamus are associated with changes in

emotional reactivity. However, the importance of these nuclei on the regulation of emotional behavior is not

due to the thalamus itself, but to the connections of these nuclei with other limbic system structures. The

medial dorsal nucleus makes connections with cortical zones of the prefrontal area and with the hypothalamus.

The anterior nuclei connect with the mamillary bodies and through them, via fornix, with the hippocampus and

the cingulated gyrus, thus taking part in what is known as the Papez's circuit.

Image of the brain showing the location of the

hypothalamus.

Hypothalamus

The Hypothalamus is a small part of the brain located just below

the thalamus on both sides of the third ventricle. Lesions of the

hypothalamus interfere with several vegetative functions and

some so called motivated behaviors like sexuality,

combativeness, and hunger. The hypothalamus also plays a role

in emotion. Specifically, the lateral parts seem to be involved

with pleasure and rage, while the medial part is linked to

aversion, displeasure, and a tendency to uncontrollable and loud

laughing. However, in general the hypothalamus has more to do

with the expression of emotions. When the physical symptoms

of emotion appear, the threat they pose returns, via the

hypothalamus, to the limbic centers and then the prefrontal

nuclei, increasing anxiety.

The Fornix and Parahippocampal

These small structures are important connecting pathways for the limbic system.

The Cingulate Gyrus

The Cingulate Gyrus is located in the medial side of the brain between the cingulated sulcus and the corpus

callosum. There is still much to be learned about this gyrus, but it is already known that its frontal part

coordinates smells and sights, with pleasant memories of previous emotions. The region participates in the

emotional reaction to pain and in the regulation of aggressive behavior.

Memory and Learning

Memory is defined as : The mental faculty of retaining and recalling past experiences, the act or instance of

remembering recollection. Learning takes place when we retain and utilize past memories.

Overall, the mechanisms of memory are not completely understood. Brain areas such as the hippocampus, the

amygdala, the striatum, or the mammillary bodies are thought to be involved in specific types of memory. For

example, the hippocampus is believed to be involved in spatial learning and declarative learning (learning

information such as what you're reading now), while the amygdala is thought to be involved in emotional memory.

Damage to certain areas in patients and animal models and subsequent memory deficits is a primary source of

information. However, rather than implicating a specific area, it could be that damage to adjacent areas, or to a

pathway traveling through the area is actually responsible for the observed deficit. Further, it is not sufficient to

describe memory, and its counterpart, learning, as solely dependent on specific brain regions. Learning and memory

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are attributed to changes in neuronal synapses, thought to be mediated by long-term potentiation and long-term

depression.

There are three basic types of memory:

1. Sensory Memory

2. Short Term Memory

3. Long Term Memory

Sensory Memory

The sensory memories act as a buffer for stimuli through senses. A sensory memory retains an exact copy of

what is seen or heard: 

iconic memory for visual, echoic memory for aural and haptic memory for touch.

Information is passed from sensory memory into short term memory. Some believe it lasts only 300

milliseconds, it has unlimited capacity. Selective attention determines what information moves from sensory

memory to short term memory.

Short Term Memory

Short Term Memory acts as a scratch pad for temporary recall of the information under process. For instance,

in order to understand this sentence you need to hold in your mind the beginning of the sentence as you read

the rest. Short term memory decays rapidly and also has a limited capacity. Chunking of information can lead

to an increase in the short term memory capacity, this is the reason why a hyphenated phone number is easier

to remember than a single long number. The successful formation of a chunk is known as 

closure. 

Interference

often causes disturbance in short term memory retention. This accounts for the desire to complete a task held

in short term memory as soon as possible.

Within short term memory there are three basic operations:

1. Iconic memory - the ability to hold visual images

2. Acoustic memory - the ability to hold sounds. Can be held longer than iconic.

3. Working memory - an active process to keep it until it is put to use. Note that the goal is not really to move the

information from short term memory to long term memory, but merely to put it to immediate use.

The process of transferring information from short term to long term memory involves the encoding or consolidation

of information. This is not a function of time, that is, the longer the memory stays in the short term the more likely it

is to be placed in the long term memory. On organizing complex information in short term before it can be encoded

into the long term memory, in this process the meaningfulness or emotional content of an item may play a greater

role in its retention in the long term memory. The limbic system sets up local reverberating circuits such as the

Papez's Circuit.

Long Term Memory

Long Term Memory is used for storage of information over a long time. Information from short to long term

memory is transferred after a short period. Unlike short term memory, long term memory has little decay.

Long term potential is an enhanced response at the synapse within the hippocampus. It is essential to memory

storage. The limbic system isn't directly involved in long term memory necessarily but it selects them from

short term memory, consolidates these memories by playing them like a continuous tape, and involves the

hippocampus and amygdala.

There are two types of long term memory:

1. Episodic Memory

2. Semantic Memory

Episodic memory represents our memory of events and experiences in a serial form. It is from this memory that we

can reconstruct the actual events that took place at a given point in our lives. Semantic memory, on the other hand, is

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a structured record of facts, concepts, and skills that we have acquired. The information in the semantic memory is

derived from our own episode memory, such as that we can learn new facts or concepts from experiences.

There are three main activities that are related to long term memory:

1. Storage

2. Deletion

3. Retrieval

Information for short term memory is stored in long term memory by rehearsal. The repeated exposure to a stimulus

or the rehearsal of a piece of information transfers it into long term memory. Experiments also suggest that learning

is most effective if it is distributed over time. Deletion is mainly caused by decay and interference. Emotional factors

also affect long term memory. However, it is debatable whether we actually ever forget anything or whether it just

sometimes becomes increasingly difficult to retrieve it. Information may not be recalled sometimes but may be

recognized, or may be recalled only with prompting. This leads us to the third operation of memory, information

retrieval.

There are two types of information retrieval:

1. Recall

2. Recognition

In recall, the information is reproduced from memory. In recognition the presentation of the information provides the

knowledge that the information has been seen before. Recognition is of lesser complexity, as the information is

provided as a cue. However, the recall may be assisted by the provision of retrieval cues which enable the subject to

quickly access the information in memory.

Long-term Potentiation

. Long-term potentiation (LTP) is the lasting enhancement of connections between two neurons that results from

stimulating them simutaneously. Since neurons communicate via chemical synapses, and because memories are

believed to be stored within these synapses, LTP and it's opposing process, long-term depression, are widely

considered the major cellular mechanisms that underlie learning and memory. This has been proven by lab

experiments. When one of the chemicals involved (PKMzeta, it will be discussed later) is inhibited in rats, it causes

retrograde amnesia with short term memory left intact (meaning they can't recall events from before the inhibitor was

given).

By enhancing synaptic transmission, LTP improves the ability of two neuron, one presynaptic and the other

postsynaptic, to communicate with one another across a synapse. The precise mechanism for this enhancement isn't

known, but it varies based on things like brain region, age and species. This will focus on LTP in the CA1 section of

the hippocampus, because that's what is well known.

The end result of LTP is a well established neural circuit that can be called upon later for memory.

LTP in the CA1 hippocampus is called NMDA receptor-dependent LTP. It has four main properties.

• Rapid induction

LTP can be rapidly induced by applying one or more brief, high-frequency, stimulus to a presynaptic cell.

• Input specificity

Once induced, LTP at one synapse does not spread to other synapses; rather LTP is input specific. LTP is only

propagated to those synapses according to the rules of associativity and cooperativity.

• Associativity

Associativity refers to the observation that when weak stimulation of a single pathway is insufficient for the

induction of LTP, simultaneous strong stimulation of another pathway will induce LTP at both pathways.

• Cooperativity

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LTP can be induced either by strong tetanic stimulation of a single pathway to a synapse, or cooperatively via

the weaker stimulation of many. When one pathway into a synapse is stimulated weakly, it produces

insufficient postsynaptic depolarization to induce LTP. In contrast, when weak stimuli are applied to many

pathways that converge on a single patch of postsynaptic membrane, the individual postsynaptic

depolarizations generated may collectively depolarize the postsynaptic cell enough to induce LTP

cooperatively. Synaptic tagging, discussed later, may be a common mechanism underlying associativity and

cooperativity.

LTP is generally divided into three parts that occur sequentially: Short-term potentiation, early LTP (E-LTP) and late

LTP (L-LTP). Short-term potentiation isn't well understood and will not be discussed.

E-LTP and L-LTP phases of LTP are each characterized by a series of three events: induction, maintenance and

expression. Induction happens when a short-lived signal triggers that phase to begin. Maintenance corresponds to the

persistent biochemical changes that occur in response to the induction of that phase. Expression entails the

long-lasting cellular changes that result from activation of the maintenance signal.

Each phase of LTP has a set of mediator molecules that dictate the events of that phase. These molecules include

protein receptors, enzymes, and signaling molecules that allow progression from one phase to the next. In addition to

mediators, there are modulator molecules that interact with mediators to fine tune the LTP. Modulators are a bit

beyond the scope of this introductory book, and won't be discussed here.

Early Phase

Induction

E-LTP induction begins when the calcium inside the postsynaptic cell exceeds a threshold. In many types of LTP,

the flow of calcium into the cell requires the NMDA receptor, which is why these types of LTP are considered

NMDA receptor-dependent.

When a stimulus is applied to the presynaptic neuron, it releases a neurotransmitter, typically glutamate, onto the

postsynaptic cell membrane where it binds to AMPA receptors, or AMPARs. This causes an influx of sodium ions

into the postsynaptic cell, this short lived depolarization is called the excitatory postsynaptic potential (EPSP) and

makes it easier for the neuron to fire an action potential.

A single stimulus doesn't cause a big enough depolarization to trigger an E-LTP, instead it relies on EPSP

summation. If EPSPs are reaching the cell before the others decay, they will add up. When the depolarization reaches

a critical level, NMDA receptors lose the magnesium molecule they were originally plugged with and let calcium in.

The rapid rise in calcium within the postsynaptic neuron trigger the short lasting activation of several enzymes that

mediate E-LTP induction. Of particular importance are some protein kinase enzymes, including CaMKII and PKC.

To a lesser extent, PKA and MAPK activation also contribute.

Maintenance

During the maintenance stage of E-LTP, CaMKII and PKC lose their dependence on calcium and become

autonomously active. They then carry out phosphorylation that underlies E-LTP expression.

Expression

CaMKII and PKC phosphorylate existing AMPA receptors to increase their activity, and mediate the insertion of

additional AMPA receptors onto the postsynaptic cell membrane. This is achieved by having a pool of nonsynaptic

AMPA receptors adjacent to the postsynaptic membrane. When the appropriate stimulus arrives, the nonsynaptic

AMPA receptors are brought into the postsynaptic membrane under the influence of protein kinases.

AMPA receptors are one of the most common type of receptors in the brain. Their effect is excitatory. By adding

more AMPA receptors, and increasing their activity, future stimuli will generate larger postsynaptic responses.

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Late Phase

Late LTP is the natural extension of E-LTP. L-LTP requires gene transcription and protein synthesis in the

postsynaptic cell, unlike E-LTP. Late LTP is also associated with the presynaptic synthesis of synaptotagmin and an

increase in synaptic vesicle number, suggesting that L-LTP induces protein synthesis not only in postsynaptic cells,

but in presynaptic cells as well. This is discussed under "retrograde messenger" below.

Induction

Late LTP is induced by changes in gene expression and protein synthesis brought about by persistent activation of

protein kinases activated during E-LTP, such as MAPK. In fact, MAPK--Specifically the ERK subfamily of

MAPKs--may be the molecular link between E-LTP and L-LTP, since many signaling cascades involved in E-LTP,

including CaMKII and PKC, can converge on ERK.

Maintenance

Upon activation, ERK may phosphorylate a number of cytoplasmic and nuclear molecules that ultimately result in

the protein synthesis and morphological changes associated with L-LTP. These chemicals may include transcription

factors such as CREB. ERK-mediated changes in transcription factor activity may trigger the synthesis of proteins

that underlie the maintenance of L-LTP. PKMzeta is one such molecule. When this molecule is inhibited in rats, they

experience retrograde amnesia (where you can't recall previous events but short term memory works fine).

Expression

Aside from PKMzeta, many of the proteins synthesized during L-LTP are unknown. They are though to increase

postsynaptic dendritic spine number, surface area and sensitivity to the neurotransmitter associated with L-LTP

expression.

Retrograde Signaling

Retrograde signaling is a hypothesis that attempts to explain that, while LTP is induced and expressed

postsynaptically, some evidence suggests that it is expressed presynaptically as well. The hypothesis gets its name

because normal synaptic transmission is directional and proceeds from the presynaptic to the postsynaptic cell. For

induction to occur postsynaptically and be partially expressed presynaptically, a message must travel from the

postsynaptic cell to the presynaptic cell in a retrograde (reverse) direction. Once there, the message presumably

initiates a cascade of events that leads to a presynaptic component of expression, such as the increased probability of

neurotransmitter vesicle release.

Retrograde signaling is currently a contentious subject as some investigators do not believe the presynaptic cell

contributes at all to the expression of LTP. Even among proponents of the hypothesis there is controversy over the

identity of the messenger.

Language and Speech

Language depends on semantic memory so some of the same areas in the brain are involved in both memory and

language. Articulation, the forming of speech, is represented bilaterally in the motor areas. However, for most

individuals, language analysis and speech formation take place in regions of the left hemisphere only. The two

regions involved are:

1. Broca's Area
2. Wernicke's Area

Broca's area is located just in front of the voice control area of the left motor cortex. This region assembles the motor

of speech and writing. For example, patients with lesions in this area:

1. Understand language perfectly

2. May be able to write perfectly

3. Seldom speak spontaneously

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Wernicke's area is part of the auditory and visual associations cortex. This region is responsible for the analysis and

formation of language content. For example, patients with lesions in this area:

1. Are unable to name objects

2. Are unable to understand the meaning of words

3. Articulate speech readily but usually nonsensically

Diseases of the Limbic System

There are several well known diseases that are disorders of the limbic system. Several are discussed here.

Schizophrenia

An increased dopamine (DA) response in the limbic system results in schizophrenia. DA may be synthesized or

secreted in excess, DA receptors may be supersensitive, and DA regulatory mechanism may be defective. Symptoms

are decreased by drugs which block DA receptors. Symptoms of schizophrenia are:

1. Loss of touch with reality

2. Decreased ability to think and reason

3. Decreased ability to concentrate

4. Decreased memory

5. Regress in child-like behavior

6. Altered mood and impulsive behavior

7. Auditory hallucinations

Symptoms may be so severe that the individual cannot function.

Depression

Depression is the most common major mental illness and is characterized by both emotional and physical symptoms.

Symptoms of depression are:

1. Intense sadness and despair

2. Anxiety

3. Loss of ability to concentrate

4. Pessimism

5. Feelings of low self esteem

6. Insomnia or hypersomnia

7. Increased or decreased appetite

8. Changes in body temperature and endocrine gland function

10 to 15% of depressed individuals display suicidal behavior during their lifetime.

The cause of depression and its symptoms are a mystery but we do understand that it is an illness associated with

biochemical changes in the brain. A lot of research goes on to explain that it is associated with a lack of amines

serotonin and norephinephrine. Therefore pharmacological treatment strategies often try to increase amine

concentrations in the brain.

One class of antidepressants is monoamine oxidase inhibitors. Mono amine oxidase is a enzyme that breaks down

your amines like norephinephrine and serotonin. Because the antidepressants inhibit their degradation they will

remain in the synaptic cleft for a longer period of time making the effect just as if you had increased theses types of

neurotransmitters.

A newer class of antidepressants is selective serotonin reuptake inhibitors (SSRI's). With SSRI's decreasing the

uptake of serotonin back into the cell that will increase the amount of serotonin present in the synaptic cleft. SSRI's

are more specific than the monoamine oxidase inhibitors because they only affect serotonergic synapses. You might

recognize these SSRI's by name as Prozac and Paxil.

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Bipolar Disorder

Another common form of depression is manic depression. Manic is an acute state characterized by:

1. Excessive elation and impaired judgment

2. Insomnia and irritability

3. Hyperactivity

4. Uncontrolled speech

Manic depression, also known as bipolar disorder, displays mood swings between manic and depression. The limbic

system receptors are unregulated. Drugs used are unique mood stabilizers.

The hippocampus is particularly vulnerable to several disease processes, including ischemia, which is any

obstruction of blood flow or oxygen deprivation, Alzheimer

s disease, and epilepsy. These diseases selectively attack

CA1, which effectively cuts through the hippocampal circuit.

An Autism Link

A connection between autism and the limbic system has also been noted as well. URL: http:/

 

/

 

www.

 

autism.

 

org/

limbic.

 

html

Case Study

Central Pain Syndrome

I was 42 years old when my life changed forever. I had a stroke. As an avid viewer of medical programs on

television I assumed that I would have physical therapy for my paralyzed left side and get on with my life. No one

ever mentioned pain or the possibility of pain, as a result of the stroke. I did experience unusual sensitivity to touch

while still in the hospital, but nothing to prepare me for what was to come.

The part of my brain that is damaged is the Thalamus. This turns out to be the pain center and what I have now is an

out of control Thalamus, resulting in Thalamic Pain syndrome, also called Central Pain Syndrome. This means that

24 hours a day, seven days a week, my brain sends messages of pain and it never goes away. I am under the care of

physicians, who not only understand chronic pain, but are also willing to treat it with whatever medications offer

some help. None of the medications, not even narcotic medications, take the pain away. They just allow me to

manage it so I can function.

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The Peripheral Nervous System

The Cranial Nerves

The 

peripheral nervous system 

includes 12 cranial

nerves 31 pairs of spinal nerves. It can be subdivided

into the 

somatic 

and 

autonomic 

systems. It is a way of

communication from the central nervous system to the

rest of the body by nerve impulses that regulate the

functions of the human body.

The twelve cranial nerves are

Olfactory Nerve 

for smell

II 

Optic Nerve 

for vision

III 

Oculomotor 

for looking around

IV 

Trochlear 

for moving eye

Trigeminal 

for feeling touch on face

VI 

Abducens 

to move eye muscles

VII 

Facial 

to smile, wink, and help us taste

VIII 

Vestibulocochlear 

to help with balance,

equilibrium, and hearing

IX 

Glossopharengeal 

for swallowing and gagging

Vagus 

for swallowing, talking, and parasympathetic actions of digestion

XI 

Spinal accessory 

for shrugging shoulders

XII 

Hypoglossal 

for tongue more divided into different regions as muscles

The 10 out of the 12 cranial nerves originate from the brainstem, and mainly control the functions of the anatomic

structures of the head with some exceptions. CN X receives visceral sensory information from the thorax and

abdomen, and CN XI is responsible for innervating the sternocleidomastoid and trapezius muscles, neither of which

is exclusively in the head.

Spinal nerves take their origins from the spinal cord. They control the functions of the rest of the body. In humans,

there are 31 pairs of spinal nerves: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal. The naming

convention for spinal nerves is to name it after the vertebra immediately above it. Thus the fourth thoracic nerve

originates just below the fourth thoracic vertebra. This convention breaks down in the cervical spine. The first spinal

nerve originates above the first cervical vertebra and is called C1. This continues down to the last cervical spinal

nerve, C8. There are only 7 cervical vertebrae and 8 cervical spinal nerves.

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Lateral cord

The 

lateral cord 

gives rise to the following nerves:

• The lateral pectoral nerve, C5, C6 and C7 to the pectoralis major muscle, or musculus pectoralis major.

• The musculocutaneous nerve which innervates the biceps muscle

• The median nerve, partly. The other part comes from the medial cord. See below for details.

Posterior cord

diagram showing human dermatoms, i.e., skin regions with respect to

the routing of their nerve connection of their afferent nerves through the

spinal cord.

The 

posterior cord 

gives rise to the following

nerves:

• The upper subscapular nerve, C7 and C8, to the

subscapularis muscle, or musculus supca of the

rotator cuff.

• The lower subscapular nerve, C5 and C6, to the

teres major muscle, or the musculus teres major,

also of the rotator cuff.

• The thoracodorsal nerve, C6, C7 and C8, to the

latissimus dorsi muscle, or musculus latissimus

dorsi.

• The axillary nerve, which supplies sensation to the

shoulder and motor to the deltoid muscle or

musculus deltoideus, and the teres minor muscle,

or musculus teres minor.

• The radial nerve, or nervus radialis, which

innervates the triceps brachii muscle, the

brachioradialis muscle, or musculus

brachioradialis,, the extensor muscles of the

fingers and wrist (extensor carpi radialis muscle),

and the extensor and abductor muscles of the

thumb. See radial nerve injuries.

Medial cord

The 

medial cord 

gives rise to the following nerves:

• The median pectoral nerve, C8 and T1, to the pectoralis muscle

• The medial brachial cutaneous nerve, T1

• The medial antebrachial cutaneous nerve, C8 and T1

• The median nerve, partly. The other part comes from the lateral cord. C7, C8 and T1 nerve roots. The first branch

of the median nerve is to the pronator teres muscle, then the flexor carpi radialis, the palmaris longus and the

flexor digitorum superficialis. The median nerve provides sensation to the anterior palm, the anterior thumb,

index finger and middle finger. It is the nerve compressed in carpal tunnel syndrome.

• The ulnar nerve originates in nerve roots C7, C8 and T1. It provides sensation to the ring and pinky fingers. It

innervates the flexor carpi ulnaris muscle, the flexor digitorum profundus muscle to the ring and pinky fingers,

and the intrinsic muscles of the hand (the interosseous muscle, the lumbrical muscles and the flexor pollicus

brevis muscle). This nerve traverses a groove on the elbow called the cubital tunnel, also known as the funny

bone. Striking the nerve at this point produces an unpleasant sensation in the ring and little fingers.

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Other thoracic spinal nerves (T3-T12)

The remainder of the thoracic spinal nerves, T3 through T12, do little recombining. They form the 

intercostal

nerves

, so named because they run between the ribs. For points of reference, the 7th intercostal nerve terminates at

the lower end of the sternum, also known as the xyphoid process. The 10th intercostal nerve terminates at the

umbilicus, or the belly button.

The 

somatic nervous system 

is that part of the peripheral nervous system associated with the voluntary control of

body movements through the action of skeletal muscles, and also reception of external stimuli. The somatic nervous

system consists of afferent fibers that receive information from external sources, and efferent fibers that are

responsible for muscle contraction. The somatic system includes the pathways from the skin and skeletal muscles to

the Central Nervous System. It is also described as involved with activities that involve consciousness.

The basic route of the efferent somatic nervous system includes a two neuron sequence. The first is the upper motor

neuron, whose cell body is located in the precentral gyrus (Brodman Area 4) of the brain. It receives stimuli from

this area to control skeletal (voluntary) muscle. The upper motor neuron carries this stimulus down the corticospinal

tract and synapses in the ventral horn of the spinal cord with the alpha motor neuron, a lower motor neuron. The

upper motor neuron releases acetylcholine from its axon terminal knobs and these are received by nicotinic receptors

on the alpha motor neuron. The alpha motor neurons cell body sends the stimulus down its axon via the ventral root

of the spinal cord and proceeds to its neuromuscular junction of its skeletal muscle. There, it releases acetylcholine

from its axon terminal knobs to the muscles nicotinic receptors, resulting in stimulus to contract the muscle.

The somatic system includes all the neurons connected with the muscles, sense organs and skin. It deals with sensory

information and controls the movement of the body.

The Autonomic System

The 

Autonomic system 

deals with the visceral organs, like the heart, stomach, gland, and the intestines. It regulates

systems that are unconsciously carried out to keep our body alive and well, such as breathing, digestion (peristalsis),

and regulation of the heartbeat. The Autonomic system consists of the 

sympathetic 

and the 

parasympathetic

divisions. Both divisions work without conscious effort, and they have similar nerve pathways, but the sympathetic

and parasympathetic systems generally have opposite effects on target tissues (they are antagonistic). By controlling

the relative input from each division, the autonomic system regulates many aspects of homeostasis. One of the main

nerves for the parasympathetic autonomic system is Cranial Nerve X, the Vagus nerve.

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Figure 1: 

The right sympathetic chain and its

connections with the thoracic, abdominal, and

pelvic plexuses. (After Schwalbe.)

The Sympathetic and Parasympathetic Systems

The sympathetic nervous system activates what is often termed the

fight or flight response, as it is most active under sudden stressful

circumstances (such as being attacked). This response is also known as

sympathetico-adrenal response of the body, as the pre-ganglionic

sympathetic fibers that end in the adrenal medulla (but also all other
sympathetic fibers) secrete acetylcholine, which activates the secretion

of adrenaline (epinephrine) and to a lesser extent noradrenaline

(norepinephrine) from it. Therefore, this response that acts primarily on

the cardiovascular system is mediated directly via impulses transmitted

through the sympathetic nervous system and indirectly via

catecholamines secreted from the adrenal medulla.

Western science typically looks at the SNS as an automatic regulation

system, that is, one that operates without the intervention of conscious

thought. Some evolutionary theorists suggest that the sympathetic

nervous system operated in early organisms to maintain survival

(Origins of Consciousness, Robert Ornstein; et al.), as the sympathetic

nervous system is responsible for priming the body for action. One

example of this priming is in the moments before waking, in which

sympathetic outflow spontaneously increases in preparation for action.

The parasympathetic nervous system is part of the autonomic nervous system. Sometimes called the rest and digest

system or feed and breed. The parasympathetic system conserves energy as it slows the heart rate, increases

intestinal and gland activity, and relaxes sphincter muscles in the gastrointestinal tract.

After high stress situations (ie: fighting for your life) the parasympathetic nervous system has a backlash reaction

that balances out the reaction of the sympathetic nervous system. For example, the increase in heart rate that comes

along with a sympathetic reaction will result in an abnormally slow heart rate during a parasympathetic reaction.

Organization

Sympathetic nerves originate inside the vertebral column, toward the middle of the spinal cord in the

intermediolateral cell column (or lateral horn), beginning at the first thoracic segment of the spinal cord and

extending into the second or third lumbar segments. Because its cells begin in the thoracic and lumbar regions of the

spinal cord, the SNS is said to have a thoracolumbar outflow. Axons of these nerves leave the spinal cord in the

ventral branches (rami) of the spinal nerves, and then separate out as 'white rami' (so called from the shiny white

sheaths of myelin around each axon) which connect to two chain ganglia extending alongside the vertebral column

on the left and right. These elongated ganglia are also known as paravertebral ganglia or sympathetic trunks. In these

hubs, connections (synapses) are made which then distribute the nerves to major organs, glands, and other parts of

the body. [1]

In order to reach the target organs and glands, the axons must travel long distances in the body, and, to accomplish

this, many axons link up with the axon of a second cell. The ends of the axons do not make direct contact, but rather

link across a space, the synapse.

In the SNS and other components of the peripheral nervous system, these synapses are made at sites called ganglia.

The cell that sends its fiber is called a preganglionic cell, while the cell whose fiber leaves the ganglion is called a

postganglionic cell. As mentioned previously, the preganglionic cells of the SNS are located between the first

thoracic segment and the second or third lumbar segments of the spinal cord. Postganglionic cells have their cell

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bodies in the ganglia and send their axons to target organs or glands.

The ganglia include not just the sympathetic trunks but also the superior cervical ganglion (which sends sympathetic

nerve fibers to the head), and the celiac and mesenteric ganglia (which send sympathetic fibers to the gut).

Information transmission

Messages travel through the SNS in a bidirectional flow. Efferent messages can trigger changes in different parts of

the body simultaneously. For example, the sympathetic nervous system can accelerate heart rate; widen bronchial

passages; decrease motility (movement) of the large intestine; constrict blood vessels; increase peristalsis in the

esophagus; cause pupil dilation, piloerection (goose bumps) and perspiration (sweating); and raise blood pressure.

Afferent messages carry sensations such as heat, cold, or pain.

The first synapse (in the sympathetic chain) is mediated by nicotinic receptors physiologically activated by

acetylcholine, and the target synapse is mediated by adrenergic receptors physiologically activated by either

noradrenaline or adrenaline. An exception is with sweat glands which receive sympathetic innervation but have

muscarinic acetylcholine receptors which are normally characteristic of PNS. Another exception is with certain deep

muscle blood vessels, which have acetylcholine receptors and which dilate (rather than constrict) with an increase in

sympathetic tone. The sympathetic system cell bodies are located on the spinal cord excluding the cranial and sacral

regions. The preganglonic neurons exit from the vertebral column and synapse with the postganglonic nerouns in the

sympathetic trunk.

The parasympathetic nervous system is one of three divisions of the autonomic nervous system. Sometimes called

the rest and digest system, the parasympathetic system conserves energy as it slows the heart rate, increases intestinal

and gland activity, and relaxes sphincter muscles in the gastrointestinal tract.

Relationship to sympathetic

While an oversimplification, it is said that the parasympathetic system acts in a reciprocal manner to the effects of

the sympathetic nervous system; in fact, in some tissues innervated by both systems, the effects are synergistic.

Receptors

The parasympathetic nervous system uses only acetylcholine (ACh) as its neurotransmitter. The ACh acts on two

types of receptors, the muscarinic and nicotinic cholinergic receptors. Most transmissions occur in two stages: When

stimulated, the preganglionic nerve releases ACh at the ganglion, which acts on nicotinic receptors of the

postganglionic nerve. The postganglionic nerve then releases ACh to stimulate the muscarinic receptors of the target

organ.

The three main types of muscarinic receptors that are well characterised are:

• The M1 muscarinic receptors are located in the neural system.

• The M2 muscarinic receptors are located in the heart, and act to bring the heart back to normal after the actions of

the sympathetic nervous system: slowing down the heart rate, reducing contractile forces of the atrial cardiac

muscle, and reducing conduction velocity of the atrioventricular node (AV node). Note, they have no effect on the

contractile forces of the ventricular muscle.

• The M3 muscarinic receptors are located at many places in the body, such as the smooth muscles of the blood

vessels, as well as the lungs, which means that they cause vasoconstriction and bronchoconstriction. They are also

in the smooth muscles of the gastrointestinal tract (GIT), which help in increasing intestinal motility and dilating

sphincters. The M3 receptors are also located in many glands that help to stimulate secretion in salivary glands

and other glands of the body.

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Nervous Tissue

The nervous system coordinates the activity of the muscles, monitors the organs, constructs and also stops input from

the senses, and initiates actions. Prominent participants in a nervous system include neurons and nerves, which play

roles in such coordination.Our nervous tissue only consists of two types of cells. These cells are neurons and

neuroglia cells. The neurons are responsible for transmitting nerve impulses. Neuroglia cells are responsible for

supporting and nourishing the neuron cells.

Types of Neurons

There are three types of neurons in the body. We have sensory

neurons, interneurons, and motor neurons. Neurons are a major class of

cells in the nervous system. Neurons are sometimes called nerve cells,

though this term is technically imprecise, as many neurons do not form

nerves. In vertebrates, neurons are found in the brain, the spinal cord

and in the nerves and ganglia of the peripheral nervous system. Their

main role is to process and transmit information. Neurons have

excitable membranes, which allow them to generate and propagate

electrical impulses. Sensory neuron takes nerve impulses or messages right from the sensory receptor and delivers it

to the central nervous system. A sensory receptor is a structure that can find any kind of change in it's surroundings

or environment.

Structure of a neuron

Neurons have three different parts to them. They all have an axon, a cell body and dendrites. The axon is the part of

the neuron that conducts nerve impulses. Axons can get to be quite long. When an axon is present in nerves, it is

called a nerve fiber. A cell body has a nucleous and it also has other organelles. The dendrites are the short pieces

that come off of the cell body that receive the signals from sensory receptors and other neurons.

Myelin Sheath

Schwann cells contain a lipid substance called myelin in their plasma membranes. When schwann cells wrap around

axons, a myelin sheath forms. There are gaps that have no myelin sheath around them; these gaps are called nodes of

Ranvier. Myelin sheathes make excellent insulators. Axons that are longer have a myelin sheath, while shorter axons

do not. The disease multiple sclerosis is an autoimmune disease where the body attacks the myelin sheath of the

central nervous system.

Case Study

A 35-year-old male in 1986 had been admitted to a hospital in Florida three weeks previous to being diagnosed, with

complaints of weakness and spasticity in the right leg, difficulties with balance, and fatigue and malaise. Tests

performed at the Florida hospital had revealed abnormalities in spinal fluid and MRI brain scan. The patient

complained of being severely depressed and anxious. He had anger at his circumstances and frequent crying spells.

One month previously he had noticed aching and loss of vision in the left eye that had since improved.

This man was diagnosed with Multiple Sclerosis. MS is a chronic, degenerative, and progressive disorder that affects

the nerve fibers in the brain and spinal cord. Myelin is a fatty substance that surrounds and insulates the nerve fibers

and facilitates the conduction of the nerve impulse transmissions. MS is characterized by intermittent damage to

myelin (called demyelination) caused by the destruction of specialized cells (oligodendrocytes) that form the

substance. Demyelination causes scarring and hardening (sclerosis) of nerve fibers usually in the spinal cord, brain

stem, and optic nerves, which slows nerve impulses and results in weakness, numbness, pain, and vision loss.

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