# Human Physiology/The Nervous System

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.

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## 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.

## General functions of the CNS

!Brain, brain stem, and spinal
cord.

When the central nervous system becomes damaged or peripheral nerves
become trapped, it can increase or decrease your internal organs
functionality, it can even affect your facial expressions, i.e. make you
frown a lot, your smile becomes lopsided, your lungs can overwork, or
underwork, the lung capacity is increased or decreased, your bladder can
fill , but you are unable to urinate, your bowels become lapsed and you
are unable to completely clear them upon each bowel movement, the
muscles in your arms, legs, and torso can become weaker and more fatty,
not from lack of use, but from the nerves that run from your spine into
them being restricted from working properly, you can suffer headaches,
earaches, sore throats, blocked sinuses. Even your ability to orgasm can
be affected.

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.

## 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 are 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 does 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 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
millimeter 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 the 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 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{width="300"} The
release of an excitatory neurotransmitter (e.g. glutamate) 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. This effect is referred to as
summation.

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.

## Summation

When excitatory synapses exceed the number 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).

`<b>`{=html}Tonic or regular spiking:`</b>`{=html} Some neurons are
typically constantly (or tonically) active. Example: interneurons in the
neostriatum.

`<b>`{=html}Phasic or bursting:`</b>`{=html} Neurons that fire in bursts
is called phasic.

`<b>`{=html}Fast spiking:`</b>`{=html} Some neurons are notable for
their fast firing rates. For example, some types of cortical inhibitory
interneurons, cells in globus pallidus.

`<b>`{=html}Thin-spike:`</b>`{=html} Action potentials of some neurons
are more narrow compared to the others. For example, interneurons in the
prefrontal cortex are thin-spike neurons.

Classification by neurotransmitter released:

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

### 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.`{width="422"}

{{-}}

### The Nerve Impulse

! animated action
potential{width="300"}
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.\" In order for an action potential to occur, it must reach
threshold. If threshold does not occur, then no action potential can
occur. 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 -55 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(+30 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**: 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). ! sodium potassium pump

```{=html}
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```

**Hyperpolarization**

When the potassium ions are below resting potential (-90 mV). Since the
cell is hyper polarized, it goes to a refractory phrase.

**Refractory phase**: The refractory period 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.

### Factors that affect sensitivity and speed

**Sensitivity**: 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. This could be caused by the lack of hormone from parathyroid glands. It could also 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 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 brain stem 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 a primary contributor to
    memory.

##### Amygdala

:   The Amygdala is a little almond shaped structure, deep inside the
    anteroinferior region of the temporal lobe, that 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 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.{width="75"}

##### 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 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 attentional 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 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 simultaneously.
Since neurons communicate via chemical synapses, and because memories
are believed to be stored by virtue of patterns of activation of these
synapses, LTP and its 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
neurons, 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

:   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.

###### 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 major
cortical 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 sequencing of
language, speech and writing. For example, patients with lesions in this
area:

1.  Are unable to understand language perfectly: they are typically able
    to understand nouns better than verbs or syntactical words and
    fragments
2.  May not be able to write clearly
3.  Usually speak in fragmented phrases and sentences, often with effort

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.  Have difficulty naming objects
2.  Have difficulty understand the meaning of words
3.  Articulate speech readily but often with distorted or unintelligible
    meaning

#### 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 an 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 these 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.

##### Bipolar Disorder

Another common form of depression is manic depression. Mania 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 mania 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.

## The Peripheral Nervous System

!The Cranial Nerves{width="250"}

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

:   I **Olfactory Nerve** for smell
:   II **Optic Nerve** for vision
:   III **Oculomotor** for looking around
:   IV **Trochlear** for moving eye
:   V **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 **Glossopharyngeal** for swallowing and gagging
:   X **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

10 out of the 12 cranial nerves originate from the brain stem (I and II
are in the cerebrum), 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.

### 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.{width="300"}

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 pollicis
    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.

### 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.

right\|frame\|**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 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, specifically the
thoracolumbar region (T1-L3). The preganglionic neurons exit from the
vertebral column and synapse with the postganglonic neurons 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.

## 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

![](Neuron.svg "Neuron.svg")

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 nucleus
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). 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.
Because different nerves are affected at different times, MS symptoms
often worsen (exacerbate), improve, and develop in different areas of
the body. Early symptoms of the disorder may include vision changes
(blurred vision, blind spots) and muscle weakness. MS can progress
steadily or cause acute attacks (exacerbations) followed by partial or
complete reduction in symptoms (remission). Most patients with the
disease have a normal lifespan.

There are different types of MS: Multiple sclerosis is classified according to frequency and severity of neurological symptoms, the ability of the CNS to recover, and the accumulation of damage.

![](Types_of_MS.jpg "Types_of_MS.jpg")

### Treating Depression

Every now and then we all feel a little blue, these feelings can be
caused by losing a loved one. Clinical depression goes much further than
just feeling down. Depression has many symptoms, including lack of
energy, abnormal eating habits (either too much or too little) and
sleeping problems (also too much or too little). Often a person can feel
worthless and have thoughts of committing suicide. 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.

## Drugs

A drug is, generally speaking, any substance that changes the way your
body works. Some drugs have a medicinal effect, and some are used
recreationally. They have diverse effects, depending on the drug. Drugs
can do anything from diminish pain, to preventing blood clots, to
helping a depressed person.

Different drugs work in different ways, called the mechanism of action,
the drugs covered here will all act on the nervous system via receptors
on different neurons. There are also drugs that change how enzymes work,
but that\'s not part of the nervous system (at least directly) and will
not be discussed here.

You\'ve probably heard the terms stimulant (excitatory) and depressant
(inhibitory). This is a broad way of classifying drugs that work on the
CNS. Depressants slow down neural function, and stimulants speed it up.

Most of the common depressants (including alcohol, benzodiazepines,
barbiturates and GHB) work on GABA receptors, although there are others.
Opiates, for example, work on mu opioid receptors and also produce
inhibitory effects, and some antipsychotics block serotonin. See the
alcohol section below to see one way this can work.

Stimulants work mostly with epinephrine, dopamine or serotonin (or a
combination of them). Many of them either mimic one, or stop them from
leaving the synapse, causing more action potentials to be fired.
Methamphetamine, discussed below, is a fairly typical stimulant drug.

### Drug Abuse

![](Phencyclidine_(PCP).jpg "Phencyclidine_(PCP).jpg"){width="60"}

Scientists have long accepted that there is a biological basis for drug
addiction, though the exact mechanisms responsible are only now being
identified. It is believed that addictive substances create dependence
in the user by changing the brain\'s reward functions, located in the
mesolimbic dopamine system---the part of the brain that reinforces
certain behaviors such as eating, sexual intercourse, exercise, and
social interaction. Addictive substances, through various means and to
different degrees, cause the synapses of this system to flood with
excessive amounts of dopamine, creating a brief rush of euphoria more
commonly called a \"high". Some say that abuse begins when the user
begins shirking responsibility in order to afford drugs or to have
enough time to use them. Some say it begins when a person uses
\"excessive\" amounts, while others draw the line at the point of
legality, and others believe it amounts to chronic use despite
degenerating mental and physical health in the user. Some think that any
intoxicant consumption is an inappropriate activity. Here are some drugs
that are abused frequently: Acid/LSD, Alcohol, various tryptamines and
phenethylamines, Cocaine, Ecstasy/MDMA, Heroin, Inhalants, Marijuana,
Methamphetamine, PCP/Phencyclidine, Prescription Medications,
Smoking/Nicotine and Steroids.

### Alcohol

Alcohol is, and has been for thousands of years, one of the most
commonly used drugs in the world. It is legal, with some restrictions
and exceptions, nearly everywhere. It is a common misconception that
somehow alcohol is \'better\' or \'safer\' than other recreational
drugs. This is simply NOT the case. Alcohol is a depressant, and as such
it has the potential to cause coma, respiratory depression/arrest and
possibly death. Compared with some other (illegal in most places) drugs
of recreational value (such as marijuana, serotonin based hallucinogens
like LSD or psilocybin) alcohol is far more toxic and has more risk of
overdose. That doesn\'t mean that moderate drinking will probably hurt
you, though, either.

Short term effects from drinking (listed roughly as they appear, and as
dosage goes up) are: decreased inhibitions and, thus, judgment, flushing
of the face, drowsiness, memory problems, severe motor impairment,
blurry vision, dizziness, confusion, nausea, possible unconsciousness,
coma, and death (due to respiratory arrest or possibly aspiration on
vomit).

Alcohol produces these effects mainly via the GABA receptors in the
brain. When GABA (or in this case alcohol) binds to it\'s receptor, it
lets either Cl- ions in, or K+ out. This is called hyperpolarization, or
an inhibitory postsynaptic potential (IPSP). It makes it harder for the
neuron to depolarize and hence harder for it to fire an action
potential, slowing neural function. At higher doses alcohol will start
to block NMDA. NMDA is involved in memory (see the long-term
potentiation section) so this is thought to account for memory
blackouts.

### Methamphetamine

In the US, medically prescribed **methamphetamine** is distributed in
tablet form under the brand name Desoxyn®, generally for Attention
Deficit Hyperactivity Disorder (ADHD) but also for narcolepsy or
obesity.

Illicit methamphetamine comes in a variety of forms. Most commonly it is
found as a colorless crystalline solid, sold on the street under a
variety of names, such as: crystal meth or crystal. Methamphetamine may
also be referred to as shards, rock, pony, crissie, crystal, glass, ice,
Jib, critter, Tina, tweak or crank. Dope may refer to methamphetamine or
other drugs, especially heroin or marijuana. The term \"speed\" can
denote any stimulant including other amphetamines (e.g. adderall),
cocaine and methylphenidate (Ritalin).

Methamphetamine can be injected (either subcutaneous, intramuscular or
intravenous), smoked, snorted, swallowed, or used rectally or
sublingually. The latter two being fairly uncommon. After
administration, methamphetamine takes from a few seconds (smoked or
injected IV) to around 30 minutes (oral) for effects to arise, lasting
around eight hours depending on the route of administration.
Effects/side effects include euphoria, anorexia, increased energy,
clenching of the jaw/grinding of teeth (bruxism), weight loss, insomnia,
tooth decay and psychosis among others.

Methamphetamine is neurotoxic to at least some areas of the brain, and
owes most of its effects to the neurotransmitters dopamine,
norepinephrine and serotonin it releases. It also blocks the reuptake of
those neurotransmitters, causing them to stay in the synaptic cleft
longer than normal.

### Marijuana

!Cannabis sativa.{width="250"}

Marijuana contains a myriad of chemicals, called cannabinoids, that have
psychoactive and medicinal effects when consumed, the major one being
tetrahydrocannabinol (THC). THC serves to mimic the endogenous
neurotransmitter anandamide (also found in chocolate) at the CB~1~
receptors in the brain. Other cannabinoids include Cannabidiol (CBD),
cannabinol (CBN) and tetrahydrocannabivarin (THCV). Although THC is
found in all parts of the plant, the flower of the female plant has the
highest concentration, commonly around eight percent. The flowers can be
used, or they can be refined. Trichomes contain most of the THC on the
flowers and can be removed by a few different methods. These removed
trichomes are called kief. Kief can, in turn, be pressed into hashish.
By far the most common way to consume any of these products is by
smoking, but it can be taken orally as well.

Cannabis has a very long, very good safety record. Nobody on record has
ever died because of marijuana, directly at least. It is estimated that
it would take 1-1.8 kilograms of average potency marijuana, taken
orally, to have a fifty percent chance of killing a 68kg human. Despite
this, the possession, use, or sale of psychoactive cannabis products
became illegal in many parts of the world in the early 20th century.
Since then, while some countries have intensified the enforcement of
cannabis prohibition, others have reduced the priority of enforcement to
the point of de facto legality. Cannabis remains illegal in the vast
majority of the world\'s countries.

The nature and intensity of the immediate effects of cannabis
consumption vary according to the dose, the species or hybridization of
the source plant, the method of consumption, the user\'s mental and
physical characteristics (such as possible tolerance), and the
environment of consumption. This is sometimes referred to as set and
setting. Smoking the same cannabis either in a different frame of mind
(set) or in a different location (setting) can alter the effects or
perception of the effects by the individual. Effects of cannabis
consumption may be loosely classified as cognitive and physical.
Anecdotal evidence suggests that the Cannabis sativa species tends to
produce more of the cognitive or perceptual effects, while Cannabis
indica tends to produce more of the physical effects.

## Review Questions

Answers for these questions can be found here

1\. The junction between one neuron and the next, or between a neuron
and an effector is called:

:   A ) A synapse
:   B ) A dendrite
:   C ) A neuotransmitter
:   D ) A ventricle
:   E ) None of the above

2\. A fast excitatory synapses follows this order:

:   A ) (1) neurotransmitter released (2) diffused across the synaptic
    cleft to a receptor protein (3) binding of the transmitter opens
    pores in the ion channels and positive ions move in.
:   B ) (1) neurotransmitter released (2) diffused across the synaptic
    cleft to a receptor protein (3) binding of the transmitter opens
    pores in the ion channels and negative ions move in.
:   C ) (1) neurotransmitter released (2) diffused across the synaptic
    cleft to a receptor amino acid (3) binding of the transmitter opens
    pores in the ion channels and positive ions move in.
:   D ) (1) diffused across the synaptic cleft to a receptor protein (2)
    neurotransmitter released (3) binding of the transmitter opens pores
    in the ion channels and positive ions move in.
:   E ) None of the above

3\. Resting potential is

:   A ) excess positive ions accumulate inside the plasma membrane
:   B ) excess negative ions accumulate inside the plasma membrane
:   C ) excess positive ions accumulate outside the plasma membrane
:   D ) both b & c
:   E ) both a & c

4\. Sensory neurons have:

:   A ) A short dendrite and a long axon
:   B ) A short dendrite and a short axon
:   C ) A long dendrite and a short axon
:   D ) A long dendrite and a long axon
:   E ) Their axons and dendrites may be either long or short

5\. \_\_\_\_\_\_\_\_blocks Acetylcholine receptor sites causing muscle
relaxation.

:   A ) Novocain
:   B ) curare
:   C ) Nicotine
:   D ) Nerve gases

6\. Transmission across a synapse is dependent on the release of
\_\_\_\_\_\_\_?

:   A ) neurotransmitters
:   B ) synaptic vesicle
:   C ) neuromuscular tissue
:   D ) receptor proteins

7\. Motor neurons take messages

:   A ) from the muscle fiber to the central nervous system
:   B ) away from the central nervous system to the central nervous
    system
:   C ) that are classified
:   D ) away from the central nervous system to muscle fiber

8\. The medulla oblongata helps to regulate which of the following:

:   A ) Breathing
:   B ) Heartbeat
:   C ) Sneezing
:   D ) Vomiting
:   E ) All of the above

9\. The nervous systems main components are what?

:   A\) The Synapses and Sprinal cord
:   B\) The neurons and the synapses
:   C\) The bain and the neurons
:   D)The brain and the spinal cord

10\. Explain what LTP does to enhance communication between two neurons,
on the postsynaptic end.

11\. Explain what LTP does to enhance communication between two neurons,
on the presynaptic end.

## Glossary

**Afferent Messages:** carry sensations such as heat, cold, or pain

**Autonomic System:** deals with the visceral organs, like the heart,
stomach, gland, and the intestines

**Axon:** the part of the neuron that conducts nerve impulses

**Cannabis:** a psychoactive drug produced from parts of the cannabis
plant

**Central Nervous System (CNS):** the system that includes the brain and
the spinal cord

**Cerebellum:** part of the brain that is located posterior to the
medulla oblongata and pons, coordinates skeletal muscles to produce
smooth, graceful motions

**Cerebrospinal Fluid (CSF):** acts a shock absorber for the central
nervous system, protecting the brain and spinal cord from injury; it
also has a high glucose content which serves as a nutritional factor

**Cerebrum** motor control, learning, speech, somatic sensory functions,
vision,hearing and more.

**Dendrites:** short pieces that come off of the cell body that receive
the signals from sensory receptors and other neurons

**Episodic Memory:** represents our memory of events and experiences in
a serial form

**Excitatory Neurotransmitter:** a neurotransmitter that acts to elicit
an action potential by opening sodium ion channels

**Longitudinal Sulcus:** separates the cerebrum in to the right and left
hemispheres

**Long Term Memory:** used for storage of information over a long time

**Long-Term Potentiation (LTP)** long term communication enhancement
between two neurons. Results in neural pathways that store memoris.

**Medulla** control center for respiratory, cardiovascular and digestive
functions.

**Myelin:** a fatty substance that surrounds and insulates the nerve
fibers and facilitates the conduction of the nerve impulse transmissions

**Multiple Sclerosis (MS):** disease that affects the CNS by causing
hardening and scarring of the myelin

**Nodes of Ranvier:** unmyelinated gaps between sections of myelin

**Peripheral Nervous System (PNS):** 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

**Pons** control centers for respiration and inhibitory functions.

**Postganglionic Cells:** have their cell bodies in the ganglia and send
their axons to target organs or glands

**Postsynaptic Cells** the cell on the receiving (second) end of the
synapse.

**Presynaptic Cell** The cell on the sending (first) end of the synapse.

**Proprioception** the sense that indicates whether the body is moving
with required effort, as well as where various parts of the body are
located in relation to each other.

**Sensory Receptor:** structure that can find any kind of change in
it\'s surroundings or environment

**Somatic Nervous System (SNS):** the 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

**Synapses:** the gap between two neurons; new synapses lead to learning

## References

<http://action.painfoundation.org/site/News2?page=NewsArticle&id=5135&security=1&news_iv_ctrl=1061>
Esther Wednesday, October 19, 2005

<http://www.neurologychannel.com/multiplesclerosis/>

<http://www.theraj.com/ms/casestudy.html>