Nervous Tissues, Chapter 11
"It's my 19th nervous
breakdown."
Mick Jagger.

Brain, spinal column and knee reflex illustrations are from "Art Explosion 40,000," copyright Nova
Development Corporation, Calabasas, CA.; used under terms of license granted to Dr. J.V. Aliff.
 

The nervous system is divided into:

1. The Central Nervous System of brain and spinal cord.
2. The Peripheral N.S. of cranial nerves and spinal nerves that conduct impulses

toward and away from organs through the voluntary Somatic N.S. and the
involuntary Autonomic N.S. The Autonomic N.S. is subdivided into the
Sympathetic N.S. that is sympathetic to activities of Flight and Fight, and the
Parasympathetic N.S. that stimulates activities surrounding digestion, relaxation
and sexual arousal.

Nerve cells or Neurons are classified in various ways. According to function, they
can be Sensory (Receptor), Interneuron (Association or Connector) and
Motor (causing action, muscle contraction). Nervous tissues have neurons and
various supporting cells called glial cells. Nervous tissues are classified as Gray
Matter if they consist of neuron cell bodies and unsheathed nerve processes. The
function of gray matter is integration of function (i.e., sensory and motor). White
Matter is mostly composed of myelin sheathed nerve cell process (axons), with no neuron cell
bodies. It serves for  long distance communication function, e.g., from the receptor
neuron to the gray matter of the spinal cord, and from a region of the spinal cord to
the gray matter of the brain. .

 Two basic cell kinds are found in nervous tissues.

1. Glial cells fill up about 50% of the space of the C.N.S. Types include astrocytes
which have processes which wrap around the capillaries of the brain and gray C.N.S.
tissues, thus forming the blood-brain barrier. See pg. 390. Unlike most neurons, they
can do mitosis and therefore are typically responsible for brain tumors
(those that originate there).

Certain solutes like glucose, nonpolar lipids like steroid hormones go through the barrier;
many polar materials do not, one example is the amino acid derivative dopamine.

a. Oligodendrocytes wrap 30+ layers of membrane around neuron cell processes
such as dendrons or axons. The wrappings become the myelin sheath.
Neurolemmocytes or Schwann cells also enclose neuron processes in myelin
sheaths and, when only one layer of membrane is applied, as unmyelinated fibers.
See page 389//390.

b. Microglia are phagocyte "janitors" derived from blood monocytes. They
protect against infection.

c. Ependymal cells line the cerebrospinal canals and ventricles; they are the remnants
of the embryonic neural tube to be described later.

2. Neurons - see below.

Neuron Structure - Given in the order of passage of a stimulus, see p. 392.

1. dendrites (root-like) - pick up a stimulus and relay resulting electrical changes to

the cell body where the nucleus resides. If, such as in a single sensory neuron
process, a dendrite is sheathed by many layers of cell membrane (myelin) of a
supporting Schwann cells, it is called a dendron (older term).
2. cell body - impulses pass by ion currents through the cell body to the axon. The

cell body may also receive a stimulus as does a dendrite.
3. axon - the single axon may be myelinated or unmyelinated. In gray matter all

neuron processes are unmyelinated. In white matter, most processes are
myelinated. The axon terminates in a knob that communicates with
another cell through a tiny space called a synapse (where a muscle cell in involved,
the knob/synapse is called a motor end plate).


 Label as above.

In 1786 Galvani discovered that frog nerves could be stimulated by electricity with
muscle contraction resulting. Hodgkin and Huxley won the 1963 Nobel Prize for
describing the electrical/ionic phenomena of the Action Potential or Wave of
Depolarization.

The "Walking the Plank" Analogy

1. Resting Potential- the normal resting potential of a neuron is a minus 70

millivolts. That means the inside of the membrane is -70 mv relative to the outside of
the membrane. See p. 398-401. The ATP powered Sodium-Potassium pump maintains
more positive ions outside the membrane than inside. A volt is a term representing
not the amount of current, but rather a relative difference in electrical charge from
one position to another.

1.      Sodium-Potassium Pump:

       Step Two - Then, some K⁺ diffuse out to hyperpolarize the membrane briefly.

Now there are more positive ions outside the cell, so the outside is charges positive
and the inside is relatively negative. The neuron can conduct an impulse.
 

Fig. 1

Let's assume that the voltage is like the plank Peter Pan had to walk under the
prodding by Captain Hook's sword, Lets say the plank is 22 steps long and on the
23rd step Peter Pan falls 80 feet into the water where the crocodiles await. Falling off
the plank is the neuron firing in this analogy.

The threshold voltage (it can change) of a typical neuron plasma membrane
(neurolemma) is about a minus -48 mv, that is +22 steps in mv from the resting
potential of minus -70 mv. The threshold voltage must be exceeded on the
positive side in order for the neuron to fire. The threshold is the end of the plank,
the resting voltage is the shipside beginning of the plank. See p. 399.

What would happen if you had a graded stimulus of plus + 10 mv, would the target membrane
fire? No, you would have taken only 10 steps toward the end, so you would not fall off.
But in this partial depolarization, would the membrane be easier to fire if it was hit quickly
with a second consecutive +15 mv impulse immediately following the first? Yes,
because the plank is now shorter and the total stimulus is +25 mv, which puts you
off the plank (-70 mv + 25 mv = -45 mv, a point below the threshold voltage of -48 mv).

Regardless whether you gave a +25 mv stimulus or a +300 volt stimulus (as in heart
resuscitation), the axon hillock of the neuron or the muscle fiber would fire.
This is called the All or None Law.  Action potentials are all or none.

Graded potentials are local depolarizations or hyperpolarizations that decrease with distance. They surround receptor regulated channels.

Notice that the total change is slightly over +100 mv (or 0.1 volt) when firing takes
place. The inside of the membrane goes from -70 mv to +30 mv (100 feet in the
analogy). At this time the positive ions outside the cell rush through open gates in the
membrane, Na⁺ gates and K⁺ gates and others, inside the membrane. This causes
the + 30 mv charge noted above.

Repolarization of the neuron occurs when Na⁺ gates close and the K⁺
rush back outside the membrane again. This causes the charge inside the membrane
to become negative again. Then the Sodium-Potassium (Na/K) pump maintains the
proper resting voltage as before. . The absolute refractory period of time (0.4 msec) is
that in which the neuron cannot be stimulated to generate another action potential.
Therefore larger neurons can carry up to 2500 action potentials per second. For smaller
neurons the absolute refractory period is 4 msec. How many times per second will the
smaller neuron fire?

Nerve impulses travel as fast as 200 meters/sec in myelinated fibers. That is
because the impulse jumps from node to node, therefore bypassing much of the
neuron membrane. This is called a wave of depolarization. See pg. 406//405.
 
 
 

Unmyelinated processes carry impulses at 20m/sec - much slower.  However, in gray
matter, impulses travel more around 0.5 m/sec.  Why slower than 20 m/sec?  That is
because synapses are involved. Another factor regulating the speed of transmission is
the diameter of the processes. Thicker fibers offer less resistance to current than do
thin fibers.

Explain which tissues, white matter or gray matter are better for short-distance
communication and association in the brain versus long distance communication
(i.e., from the spinal cord to a finger muscle.)

Botulism toxin, e.g., from poorly canned mushrooms,  prevents the release of Ach into the
motor end plate. What happens then?

The Synapse - See pg. 409.

The synapse is the meeting of two neurons where transmission occurs electrically or chemically. The electrical synapse includes the gap junctions between cardiac muscle cells. Ion currents pass through channels from one cell to another.

Chemical Synapse

The synaptic cleft is the tiny space between, for instance, an axon knob and the cell body or dendrite of another neuron, or the cell body of a muscle cell. The synapse cannot be crossed by ions, so another mechanism is involved which slows things down a bit.

An action potential or wave of depolarization  sweeps down an axon
toward a knob (it's like the doors of mall stores opening on the day after Christmas).
Axon potentials can only be generated in axons.

Positive Sodium and Potassium ions rush in until they reach the axon ending (knob)  where
Ca⁺⁺ enter the knob and cause vesicles containing neurotransmitters to be dumped
into the synapse and bond on to receptors on the postsynaptic membrane of the next
neuron or muscle cell in line.

Graded potentials - these are waves of depolarization generated in unsheathed dendrites
and cell bodies. They are called graded because they have a value. Graded potentials
may summate and cause the axon hillock to fire off an action potential (see temporal and
spacial summation) above. They may be positive (depolarizing) or negative (hyperpolarizing)
in nature. Graded potentals are created in dendrites and cell bodies (soma). When these ion currents
move to the axon hillock or triggering point of the neuron, an action potential is generated
down the axon.

NEUROTRANSMISSION and POSTSYNAPTIC MEMBRANE POTENTIALS

Neurotransmitter Chemicals  - See pg. 413-417.

1. Acetylcholine/Ach - the neuromuscular transmitter. Also is present in autonomic
ganglia and the brain.

2. Amino acids - glycine (the simplest amino acid) and GABA are inhibitory;
glutamic acid and aspartic acid are excitatory in the brain.

3. Amino acid derivatives (biogenic amines) -

Metabolic Paths:

 a. Tyrosine ---> Dopa ---> Dopamine/DA ---> Norepinephrine/NE
 ---> Epinephrine/Ep

 b. Tryptophan ---> Serotonin/ST (also melatonin)

4. Neuropeptides - are short chains of 2-40 amino acids. Examples include moderating
endorphins in the spinal cord and enkephalins in the brain, and Substance P in the
pain neuron synapses.

See  http://www.benbest.com/science/anatmind/anatmd10.html

Neuroexcitation or Neurofacilitation - See pg. 419.

Neurotransmitters may be neuroexciters by causing depolarization of the postsynaptic
membrane (shortening the plank); examples are Ach (acetycholine) in skeletal muscles,
NE (norepinephrine), Epinephrine (adrenaline) and DA (dopamine). Therefore,
chemically-gated channels open and create excitatory postsynaptic potentials (EPSP).
By being secreted onto an neuron cell body postsynaptically, neuroexciters will be
secreted onto the target cell dendrite or cell body and cause it to depolarize. Then it
will send an impulse to its axon and synapse(s) as described above.

Botulism toxin inhibits the release of Ach onto muscle. What happens then?

Neuroinhibition

On the other hand, some neurotransmitters may be neuroinhibitors by causing
hyperpolarization of the postsynaptic membrane by raising (more negative)  the r
esting voltage or by lowering the threshold (more positive) - both lengthen the plank!
 This is called neuroinhibition. Neuroinhibitors include GABA, glycine, and Ach acting
on heart muscle. Therefore, any hyperpolarizing stimulus is inhibitory (a good example
is glycine and GABA which open Cl^- gates which allow Cl^- to leak inside the neuron
process). Any leakage of K⁺ out of the membrane will cause hyperpolarization also.
Neuroinhibitors thereby create inhibitory postsynaptic potentials (IPSP's).

Types of Neurofacilitation

Neurofacilitation occurs when target membranes become depolarized to some extent.
Many synapses may secrete neuroexciters on to one neuron, causing it to summate the
charges and fire when they collectively exceed the threshold. This is called
spatial summation. Many synapses can dump their neuroexciters onto a target
neuron and get it to fire the same way. When one neuron and its axon repeatedly
fire with the action potentials arriving close in time "on the heels" of previous stimuli
and the axon repeatedly releases its neuroexciters, the neurofacilitation of the
postsynaptic membrane is called temporal summation.
 

Presynaptic Membrane Potentials

There are also presynaptic inhibitory and excitatory potentials. The well known example
of the inhibitory presynapatic membrane potential is the endorphin secreting neuron which
inhibits the release of substance P neuroexciter of pain neurons. See figure 4.

Presynaptic and postsynaptic neuroinhibitors include glycine for muscle and GABA
in the brain, both open Cl- channels. Epilepsy which is an uncontrolled electrical storm
of excitatory potentials which spread through the brain, can be treated by medications
which increase GABA.

Figure 4

Removal of Neurotransmitters from the Synaptic Cleft

After an impulse is transmitted across the synapse, the neurotransmitter Ach is cleaned
up by the enzyme Ach-esterase. Mono-amine oxidases (for NE, DA and ST) regulate
neurotransmitter concentrations within the axon terminal.

Ach stimulates skeletal muscle but inhibits cardiac muscle. How so?

Neurotranmitters and Medicine

Clinical depression, either endogengenous (biological) or exogenous
(environmental: depression is a natural reaction to a hostile environment)
is characterized by decreases of NE, dopamine, and Serotonin in the brain.
Neurological activities are slowed as a result. Drugs are administered that
subtly increase NE, Serotonin and Dopamine. Monoamine oxidase inhibitors
(DA, ST and NE) are used for the treatment of acute depression. For a chronic
depression,  antidepressants such as Prozac specifically increase Serotonin in
the brain by inhibiting its reabsorption (ST reuptake inhibitor) from the
synaptic cleft.

Manic depressive syndrome is an inherited syndrome in which there are cycles
of  manic, impulsive behavior, followed by depression a month later (approx.).
During the manic phase, there is an oversupply of excitatory neurotransmitters in
the brain (DA and NE, primarily). Many famous authors and artists are manic
depressives. They may commit suicide during the impulsive, manic phase or in the
depressive phase. Many clinically depressed people talk of suicide or feel that they
are possessed by daemons.

Many poisons are Ach-esterase inhibitors that allow neurotransmitters to stay in the
synapse; therefore, the next cell (muscle) continues to depolarize and paralysis
results. Many insecticides and nerve gases operate this way.

Alzheimer's disease is characterized by the loss of neurons secreting Ach in the basal
nuclei and related areas of the higher brain. Why isn't increasing Ach a cure for
Alzheimers?

Explain how L-Dopa became a miracle drug and then flopped (Have you seen the
movie "Awakening"?)

Neurotransmitter/Drug Interactions

1. Ethyl alcohol generally depresses the metabolic activity of all neural cells.

Any amount increases reaction times, drivers!
2. Marijuana - decreases Ach in brain, increases serotonin.
3. Cocaine - increases dopamine secretions by competitively inhibiting

(binding to the transporter protein, thereby occupying ) DA reuptake
by the synaptic knob, resulting in a feeling of well being and power because
the pleasure centers of the brain are increasingly stimulated. Is cocaine addictive
physiologically? The key is treating cocaine addiction is to discover a chemical
that blocks the DA reuptake receptor.
4. Heroin/Opiates/Morphine - mimic the activity of the body's own painkilling

neurotransmitters, the dynorphins, endorphins and enkephalins that bind to mu
receptors. Interestingly, 25 years ago, the mu opiate receptor was discovered
before the body's own pain killing neurotransmitters were. At that time, it was
discovered that naloxone blocks the mu receptor. Naloxone is of value in preventing
an addict from "falling off the wagon."
5. Valium - mimics effects of GABA.
6. "Speed" or amphetamines - also competively inhibit DA reuptake.

 

Because memory is linked neurologically to the pleasure centers, an addict may
"fall off the wagon"and feel craving if they see a wine glass or interact with the
people that they did drugs with.

There are physiological addiction and psychological addiction. The body is a
neurotransmitter factory. If an exogenous source (drug) mimics or replaces
an adequate supply or oversupply of neurotransmitter, the body will cut back
on its own production of the neurotransmitter. Eventually, the physiological
addiction will cause the addict to take drugs just to get feel normal.

Back in the 1950s, opiate (general) addiction was treated by throwing the
addict in a padded cell and taking away anything that they could kill themselves
with - called the "cold turkey" treatment. This was a sudden and total withdrawal
from the drug. Patients screamed with pain and begged the attendants to kill them.
Explain why.

If the current trend in drug-related incarcerations in the USA, says Newsweek
(2-12-01) continues, by 2050, the number of people in prison will exceed that
of the number of people outside
 

1. Diverging circuit - an impulse from one axon is spread out to many others.
An example is a single motor neuron in the brain controlling many motor neurons
in the spinal cord.

2. Converging circuit - many neurons feed impulses to a small area of the brain,
i.e., the vomiting center of the medulla oblongata receives sensory input from the senses of
the stomach wall causes by distention or irritation, smell, equilibrium, and vision; a single
motor neuron may be controlled by many other neurons from various C.N.S. regions.

3. Reverberating circuit - impulses are relayed back to the originating neurons,
thus continuing the duration of the impulses. This is useful in maintaining wakefulness.

4. Parallel after-discharge circuit - specially designed to enhance the summation
of inhibitory or excitatory potentials.

NERVE HEALING

As long as the cell body of the neuron is intact, the old cell can regrow an axon.
Schwann cells form tunnels through which axons grow. Once neuron cell bodies
die, there is no hope of regeneration. Using nerve growth factor,
scientists have bridged breaks in rat spinal cords, reconnecting gray matter and
white matter. Some improvement in limb movement is seen. Why is total
recovery not possible?

Study Questions

1. Describe the transmission of an impulse through a neuron.
2. Describe synaptic neurotransmission. Compare neuroexcitation with
   neuroinhibition.
3. Describe the physiological addiction to heroin and nicotine at the synaptic and chemical levels.
4. Compare and contrast depression and manic depression.
5. Compare a muscle twitch graph and a membrane depolarization graph.
6. If a patient took MAOIs and ate a lot of  foods like red wine and cheese containing
   tyrosine, what would happen?
7. Describe the principle of Prozac action.
8. Compare and contrast spacial and temporal summation.

 Email:jaliff @ gpc.edu