Neurophysiology leture (3)
Prof. Eman Al-Khateeb
Done by: Zaid I. Wakileh
 In this lecture we will discuss the graded potential in NMJ and CNS
synapses with their neurotransmitters.
 Action potential is usually used in the periphery and not the CNS.
 In the CNS the Graded/Electrotonic potential predominates as we
need it for higher intellectual functions.
 Graded Potential
In the CNS, each neuron receives about 200,000 nerve endings
In the spinal cord, neurons that have to do with muscle contraction receive
about 10,000 nerve endings.
85% of the nerve terminals end on dendrites on the next neuron and about
10-15% end on the soma.
If the action potential is the only one present then it would be very hard to
receive information from this huge number of neurons and interpret them.
Therefore, we need the graded potential in the CNS.
We know that the graded potential will eventually fire an action potential
that travels along the whole length the axon and reaches the nerve
endings.
 Major Function of the Graded Potential:
1) Higher intellectual functions (thinking, retrieval, memory …etc.)
which would be very hard to deal with using action potential.
(Retrieval : ability to remember something after you memorized it)
2) Vision, as the retina uses graded potential much more than it uses
the action potential. We have cones only for 3 colors blue, green,
red. If action potential is to be used then we would be able to see
these 3 principal colors only. However, we can see the pink, gray,
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dark blue and light blue (mixed colours) due to partial stimulation
and summation of two or three cones.
 Some characteristics of the graded potential :
1) Unlike Action potential it can summate (temporal and spatial
summation)
2) It can be :
excitatory (depolarizing, increases the membrane potential and if
it reaches threshold it fires an action potential)
Inhibitory (Hyperpolarization)
 Are there any other places where graded potential is used? (other
than the CNS)
Of course, the end plate potential at the neuromuscular junction
(motor end plate) is a graded potential.
 End plate potential:
The end plate potential is much lower than action potential in magnitude
(subthreshold activity) and if it reaches threshold it fires an action
potential.
 So, why study the end plate potential??
The end plate potential is good model to what happens in the CNS
and it’s much easier to study the neuromuscular junction. As:
a) Synapses in the brain and spinal cord are hard to study as each
neuron in the CNS has got at least two or three neurotransmitters or
neuromodulators.
b) Whatever applies to NMJ can be applied to the synapse: Ca2+
entrance, realease of the vesicles, attachment to receptors,
activation of 2ry messenger … however, in the brain things are a bit
more complicated
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Neurotransmitter Vs. Neuromodulator
 Neurotransmitters : instant action that persists only for a short
period of time (for both motor like moving your hand from an area
of danger or sensory like when touching a hot object  fast
response)
 Neuromodulators : are these chemical substances that alter neuronal
activity by exciting or inhibiting a neuron for long periods of time like
weeks, months or even years.(intelligence, memory, learning,
thinking … etc.). these more effective than neurotransmitters and
therefore more dangerous to manipulate
 measuring the end plate potential:
In electrophysiological studies experimenrs are very hard and tedious to
prepare as measurements are in microvolts and millivolts. Moreover, we
have electrical noise from the surrounding (light bulbs, air-conditioning
systems … etc.) which is usually high. So, if we have viable tissue in resting
condition that gives electrical activity high enough to be recorded that
would be great.
Measurements are done using microelectrodes (extremely thin glass
pipette with a tip that measures a few microns) that are introduced to the
neuromuscular junction under microscope.
At “resting” state the neuromuscular junction is never resting. Actually it
has some electrical activity called “MINIATURE END PLATE POTENTIAL”
(exactly same shape and characteristic features of end plate potential but
with smaller amplitude)
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If you move 2 mm away from the NMJ you won’t be able to record the
miniature end plate potetntial. (i.e miniature end plate potential is a major
characteristic of NMJ)
 Cause of the miniature end plate potential:
Spontaneous release of a SINGLE acetylcholine-containing vesicle from the
nerve ending. (Single vesicle contains about 10,000 Acetyl-choline
molecules). This might be due to excessive synthesis of Acetylcholine in the
nerve ending so it gets rid of the excess spontaneously.
 The miniature end plate potential’s amplitude is about 0.5 millivolt
while the action potential’s amplitude is about 50 millivolts and it
needs about 50-60 vesicles.
 Three aspects of the miniature end plate potential have been
studied:
1- Amplitude
2- Frequency
3- Half decay time
This miniature end plate potential is the one used in studies
concerning drug effects and electrolyte disturbances.
 Some applications:
a) Drug or herb applied to the resting NMJ  the frequency increases
(5 per second to 15 per second or a 200 times increase )  this drug
can be used in treating myasthenia gravis.
b) Drug applied to the resting NMJ  decrease the frequency this
drug can be used to treat epilepsy (excessive discharge) and to relax
muscles.
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c) Drug applied to the resting NMJ  increases half decay time
(decreases acetylcholinesterase activity )  can be used to treat
myasthenia gravis.
 Synapses
Back to the Synapses of the CNS … same set up as the NMJ but each end of
the neuron has 2-3 different neuromodulators or neurotransmitters.
 We have two types of Synapses:
1) Electrical (Gap junctions): about 0.01% in the CNS. In the
Olfactory cortex.
(it is also found in the syncytium of the heart and in the intestine)
We don’t need this kind of synapse in the CNS as it allows for
bidirectional conduction which is not compatible with our
compartmentalized brain (each part has a separate function)
2) Chemical: about 99.9% in the CNS. This type is unidirectional.
Here once the ligand binds to its specific receptor it’s going to
make changes in the post-synaptic cell. These changes start with
the activation of a second messenger which results in either of the
following:
a) Opening/closing a channel
b) Activation of an enzyme
c) cGMP/cAMp activation
d) Altering gene transcription and protein formation causing
permanent changes in the neuron (most important as it is the
basis of the intelligence, memory, thinking and learning)
e.g. like knowing the major mathematical procedures
(addition, subtraction, division, multiplication), name of your
parents.
This is what makes us “higher animals” … without it we’re just
like reptiles.
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 CNS neurotransmitters :
In the brain we have about 50 well-proven neurotransmitters and another
150 are still under investigation (amino acids, steroids, digestive hormones
and enzymes like gastrin and cholecystokinin)
major excitatory neurotransmitter in the brain  Glutamate
major inhibitory neurotransmitter in the brain  GABA (Gamma Amino
Butyric Acid)
major excitatory neurotransmitter in spinal cord  thought to be
Glutamate
Major inhibitory neurotransmitter in the spinal cord  Glycine
 GABA:
GABA inhibits functions of the brain.For example; if you are
hyperactive/anxious GABA will reduce this effect. If you are unable to sleep
GABA will try to suppress the functions of the brain that would put you to
sleep.
Due to its inhibitory effects, many drugs have been developed to increase
GABA like (sleeping pills, valium, anti-anxiety, barbiturates, alcohol).
Note: Diazepam(Valium) is said to have a “GABA potentiating effect” and,
therefore, used as an anti-epileptic drug.
- GABA has two types of receptors:
1) Alpha receptors opens chloride channels. ( chloride is more
available outside, it flows inwards making the cytoplasm of the
neuron more negative  inhibition/hyperpolarization)
diazepam/barbiturates/alcohol – most drugs work on this
receptor
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2) Beta receptors  opens the potassium channels. ( K+ flows
outside making the inside more negative
hyperpolarization/inhibition)
few drugs work on this receptor
 Glycine:
- Strychnine: this a poison used by farmers as a pesticide and by
hunters of fur-coated animals (to kill the animals or to kill the
fungi/bacteria and get better crops). These people are usually
ignorant of the effects of this poison and, therefore, don’t use the
necessary protective equipment like gloves and masks therefore
they are exposed to high concentrations on strychnine. (Through
inhalation and skin contact).
Strychnine is inhibitory to glycine (anti-glycine drug) and as we
know glycine is an inhibitory neurotransmitter … therefore …
deletion of inhibition  uninhibited excitation arising in the
spinal cord leading to muscle spasm (spasm of respiratory
muscles  needs ventilator , spasm of back muscles  the
patient will arch upwards when lying supine).
The spasm is so bad that the patient might rupture a muscle or
break a bone.
- So the characteristic features of strychnine poisoning:
the patient is CONCIOUS , in severe pain with respiratory distress
and full spasm of skeletal muscles.
 Acetylcholine:
- Secreted from gigantocellular nuclei whose fibres project into the
cerebral cortex
- Major neurotransmitter responsible for memory, intelligence and
thinking.
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- this can be proven by the fact that Alzheimer patients lose their
memory and thinking)

1)
2)
3)
3 neurotransmitters that control mood, behavior and personality:
Dopamine (from substantia nigra)
Norepinephrine (locus cereleus)
Serotonin (Raphe nucleus)
- Norepinephrine and dopamine : staying alert, euphoric and a
sense of well-being
- Serotonin: has a calming effect, gives you a feeling of satisfaction
and well-being , you don’t need any further entertainment
- We need a balance between these three types to get the best
ideal mood situation.
- Females are more liable to get a disturbance in these
neurotransmitters
- Marjuna affects these three (altering mood)
AMPHETAMINE
- It is a medicated drug used for narcolepsy patients, people who sleep
whenever they are sitting quiet with low brain input(e.g. attending a
lecture, watching his favorite movie)
- Unfortunately, it is abused by medical students preparing for the
board exams.
- Typically these students are in their late twenties or early thirties and
so start gaining bit of weight.
- Amphetamine gives them energy and makes them alert. So, they:
a) can memorize more
b) don’t like to sleep
c) lose their appetite (helps them lose weight)
d) become euphoric.
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That’s why it looks ideal for board exam students. However,
manipulating the chemistry of the brain is not advisable unless
perfectly needed as it may have debilitating effects. (This doesn’t
only apply to amphetamine but also to antidepressants as some ppl
might get well and others might commit suicide when they use them)
FOOD:
- Food, as well, can affect these 3 neurotransmitters.
- If you want to calm down  eat CARBOHYDRATES to raise serotonin
(as tryptophan found in carbohydrates is used by the brain to
synthesize serotonin/
5-hydroxytryptamine)
- If you want to be alert and more excited  eat MEAT/PROTIEN
- HOWEVER, altering neurotransmitters in your brain by food is SHORT
LIVED(lasts about 2-3 hours only)
- So … after eating a meal you’ll always feel a bit tired or exhausted as
blood is going to the GIT, but this lasts only for a few minutes.
However, if you experience this calming effect for few hours it’s most
probably due to the increase in serotonin by carbohydrates.
- Chocolates and Mansaf raise all three neurotransmitters.

-
Glutamate/Glutamic acid
It’s a negatively charged amino acid with two carboxyl groups.
About 80% of the brain is thought to be releasing glutamate.
It has a very complicated receptor called the NMDA receptor(Nmethyl D-aspartate)
- Usually, neurotransmitters’ receptors can function as either ligand
gated or voltage gated receptors, but the glutamate receptors
function as both.
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- It has 5 binding sites, and it can bind:
1) Glutamate
2) Glycine (although inhibitory)
3) Magnesium
4) Zinc
5) PCP (Angel dust, phencyclidine)
PCP is an abused drug that works on the glutamate receptors
(80% of the brain). It causes an excessive stimulation of the
cerebral cortex  brings back memories  hallucinations and
out of body experience.
- In some cases, Glutamate causes long-term potentiation of the
neurons (weeks, months, years)  this has to do with learning
(when you learn how to drive a car), thinking, memory.
(remember that acetylcholine has to do with INTELLIGENCE AND
PROBLEM SOLVING)
- VERY IMPORTANT NOTE: if glutamate is found extracellulary it is
toxic to neurons. Therefore, in stroke patients drugs that can be
given to these patients in the first 30 minutes to inhibit glutamate’s
desctructive effects are being developed. (to decrease the damage)
“Do not listen to those who weep and complain, for their disease is contagious”
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