Download LESSON 3.2 WORKBOOK

LESSON 3.2 WORKBOOK
How do our neurons communicate
with each other?
This lesson introduces you to how one neuron communicates with another neuron during the process of synaptic transmission. In this lesson you will learn how the
electrical signal of the action potential is converted into
a chemical signal at the nerve terminal, and how this
chemical signal crosses the small gap, the synapse,
between the presynaptic and the postsynaptic neuron.
Getting pain to the brain
Pain pathways deliver information about painful stimuli (nociceptive information) using an ascending pathway that travels from the nociceptive receptors in the periphery to the brain. The pathway has four important neurons, each of which plays a different role in transmitting and interpreting the painful signal (Figure
2):
• The first, or primary, neuron is at the very beginning of the pathway. The end of its dendrites in
the periphery is where the nociceptive stimulus is first encountered. Its presynaptic terminal is
in the spinal cord and connects with…..
Wo r k b o o k
Lesson 3.2
•
The dendrites of the second neuron, which is located in the spinal cord. This neuron gathers
nociceptive information from several primary neurons into distinct pathways that ascend in the
white matter of the spinal cord. Their presynaptic terminals are in the thalamus and connect
with……
•
The third neuron, which is located in the thalamus. The thalamus is like a post office that gathers information and sends it to the right place in the cortex. So their presynaptic terminals are in
the cortex where they connect with…
•
Neurons in region of the cortex that deals with receiving sensory information about pain
(somatosensory cortex). Within the cortex these neurons also communicate with cortical areas
having other information about the environment and emotion, so that the body can initiate a
response.
Now that we know about the four neurons involved in getting pain information to the brain, let’s focus on
how the neurons communicate with each other at the synapses between them.
What are the four neurons involved in getting
pain to the brain? Where are they and what
role do they play in the pathway?
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77
LESSON READING
An introduction to synaptic transmission
DEFINITIONS OF TERMS
Neurotransmitters – chemicals
that are released by the axon
terminal and convey the message
across the synapse to another cell.
Postsynaptic potentials – small
changes in voltage (membrane
potential) due to the binding of
neurotransmitter.
Receptors – proteins that contain
binding sites for particular neurotransmitters.
For a complete list of defined
terms, see the Glossary.
Synaptic transmission is the major way that neurons communicate with each other across the small gap
between the presynaptic site and postsynaptic site called the synaptic cleft. When we left the presynaptic
terminal, an electrical signal — the action potential — had traveled down the axon. However the action
potential, being electric, can’t jump the synaptic cleft between the pre- and postsynaptic sites. To transmit
the message to the postsynaptic site the neuron must convert the electrical signal to a chemical one. This
chemical signal is carried by neurotransmitters – chemicals that are released when the axon terminal is
stimulated by the action potential.
Sensory neuron Projec'on neuron Motor neuron Interneuron Figure 2: The synapses in the pain pathway. The synapses in the
pain pathway allow for modulation of pain stimuli. The first synapse
is in the periphery, where nociceptors are initially activated. The
second synapse is in the spinal cord. The third synapse is in the
thalamus (not shown here) and the fourth synapse is in the cortex.
The neurotransmitters diffuse
across the synaptic cleft to the
postsynaptic site where they bind
to specific receptors that recognize them on the postsynaptic
membrane. Once the neurotransmitter has bound to the receptor it
can produce a postsynaptic potential – a brief depolarization or
hyperpolarization in the postsynaptic membrane that happens
because the neurotransmitter
receptors themselves are associated with ion channels.
If enough postsynaptic potentials occur, the membrane may be pushed toward or away from threshold,
depending on whether the membrane has depolarized or hyperpolarized, increasing or decreasing the
likelihood of the postsynaptic neuron firing an action potential and sending the signal down its axon to
another synapse.
Since there are obviously several steps involved in synaptic transmission, let’s investigate each one in
more detail. We’ll start our more detailed discussion of synaptic transmission by taking a closer look at the
synapse.
Wo r k b o o k
Lesson 3.2
How is synaptic transmission different from
the action potential? Compare where the two
signals occur and how the signal is sent.
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78
LESSON READING
Why do you think mitochondria are located in
the presynaptic terminal?
The Synapse
DEFINITIONS OF TERMS
The word synapse was coined in 1897 by the British physiologist
Sir Charles Sherrington (Figure 3) from the Greek word synapo,
which means “to clasp”. Using only a light microscope, Sherrington
could not see the actual point of communication between neurons, but his experiments had shown that transmission can only
occur in one direction (from what we now call the presynaptic cell
to the postsynaptic cell). Sherrington even correctly inferred that
the sending (presynaptic) and receiving (postsynaptic) cells do not
actually touch each other.
Presynap)c cell Synaptic vesicles – small spherical membranes that store neurotransmitters and release them
into the synaptic cleft
Microtubule Axon Mitochondrion Presynap)c membrane Postsynap)c membrane For a complete list of defined
terms, see the Glossary.
Figure 3: Sir Charles Sherrington
(1857 – 1952). For his work, he
was awarded the Nobel Prize for
Physiology or Medicine in 1932.
Postsynap)c cell Figure 4: Structure of a typical synapse. The presynaptic
membrane faces the postsynaptic membrane. Notice that
the presynaptic cell contains both large and small synaptic
vesicles, mitochondria and microtubules. Notice that the
postsynaptic membrane contains receptors sites that will
bind neurotransmitter.
Figure 4 illustrates a synapse. The presynaptic membrane, located at the end
of the axon terminal, faces the postsynaptic membrane, located on the neuron
receiving the information. These two
membranes face each other across the
synaptic cleft, a gap that varies in size
from synapse to synapse but is usually
around 20 nanometers (nm) wide.
The presynaptic terminal
As you may have noticed in Figure 4, the axon terminal contains two prominent structures: mitochondria
and synaptic vesicles. (We can also see the microtubules, which as you will remember are responsible
for transporting the mitochondria and vesicles from the cell body where they are made to the terminal.)
Because the terminal is often swollen to contain all this material it is often called the terminal ‘button’ or
more precisely ‘bouton’, which is simply button in French.
Wo r k b o o k
Lesson 3.2
Recall from Unit 2 that vesicles are small, hollow, beadlike structures that are transported down the axon
from the cell body. In the synaptic terminal most of them are filled with neurotransmitters and become
synaptic vesicles. Axon terminals can contain as few as a few hundred and as many as nearly a million
synaptic vesicles.
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79
LESSON READING
The postsynaptic terminal
The picture in Figure 5 was taken with a very
high resolution electron microscope, and shows
that the postsynaptic membrane appears somewhat thicker and more dense than the membrane elsewhere. This increased density occurs
because the postsynpatic membrane is loaded
with neurotransmitter receptors – specialized
proteins that detect the presence of neurotransmitter in the synaptic cleft because the neurotransmitters bind to them very specifically.
What are neurotransmitters?
Figure 5: Electron micrography of an synapse.
This photography shows a cross section of a
synapse. The axon terminal is filled with synaptic
vesicles (upper left corner). The postsynaptic
membrane on the dendritic spine appears thicker
and denser than the other membranes; this is
due to the presence of receptors.
Neurotransmitters are the chemicals neurons release in order to communicate with other cells. Scientists
first thought that only a few chemicals were involved in neurotransmission, but we have now identified over
100 different neurotransmitters. Fortunately, most of them conveniently fall into a small number of chemical
classes. See Box 3.1 for descriptions of your body’s primary neurotransmitters.
BOX 3.1: Your Neurotransmitters
There are more than a hundred different neurotransmitters, with more being discovered all the time.
Scientists are finding that many hormones can also play the role of transmitter as well. Here are some
the neurotransmitters your brain uses every day:
Acetylcholine (ACh) gets us going. It excites cells, activates muscles, and is involved in wakefulness,
attentiveness, anger, aggression, and sexuality. Alzheimer’s disease is associated with a shortage of
acetylcholine.
Glutamate is a major neurotransmitter that excites other neurons. It is dispersed widely throughout the
brain. It’s involved in learning and memory.
GABA (gamma-aminobutyric acid) is your brain’s main inhibitory neurotransmitter. It slows everything
down and helps keep your systems in balance. It helps regulate anxiety.
Epinephrine, also known as adrenaline, keeps you alert and your blood pressure balanced, and it
jumps in when you need energy. It’s produced and released by the adrenal glands in times of stress.
Too much can increase anxiety or tension. Norepinephrine (noradrenaline) is a precursor and has
similar actions.
Wo r k b o o k
Lesson 3.2
Dopamine (DA) is vital for voluntary movement, attentiveness, motivation and pleasure. It’s a key player
in addiction, so we’ll discuss it again in Unit 5.
Serotonin helps regulate body temperature, memory, emotion, sleep, appetite, and mood. Many antidepressants work by regulating serotonin.
What neurotransmitters have you heard of
before and in what context?
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80
LESSON READING
Release of neurotransmitter
When action potentials are conducted down the axon and enter the presynaptic terminal, something
happens inside the terminals – a number of small synaptic vesicles spill their contents into the synaptic
cleft (Figure 6).
DEFINITIONS OF TERMS
2. Exocytosis – process by which
the contents of membrane bound
vesicle are released to the exterior
through fusion of the vesicle membrane with the cell membrane.
For a complete list of defined
terms, see the Glossary.
3. 4. 1. 5. 6. Figure 6: Steps involved in synaptic transmission. See
text for descriptions, then write your own summary.
How does an action potential cause synaptic vesicles to release neurotransmitter
into the synaptic cleft? The process begins when an action potential invades the
presynaptic terminal (Figure 6: Step 1).
Then, some of the synaptic vesicles closest to presynaptic membrane become
‘docked’ at a region in the presynaptic
terminal called the ‘active zone’. Docking
happens when clusters of proteins on the
outside of the synaptic vesicle attach to
other proteins located on the inside of the
active zone. Once they are docked, synaptic vesicles are ready to release their
neurotransmitter into the synaptic cleft.
Synaptic vesicles only release their neurotransmitter when the action potential tells them to. How does
this happen? We need to introduce another player located at the presynaptic terminals — the voltagegated calcium channel. Voltage-gated calcium channels are similar to voltage-gated sodium channels
in that they only open when the membrane depolarizes. They are different from voltage-gated sodium
channels because they are permeable to calcium ions (Ca2+), not Na+ ions. Like Na+ ions, calcium ions
(Ca2+) are located in highest concentration in the extracellular fluid, so when an action potential arrives
at the presynaptic terminal and depolarizes the membrane, the calcium channels open and Ca2+ floods
into the presynaptic terminal, propelled by the forces of diffusion and electrostatic pressure as we talked
about in Lesson 2.2 (Figure 6: Step 2).
Wo r k b o o k
Lesson 3.2
The entry of Ca2+ into the presynaptic terminal is an essential step in synaptic transmission because it
gives the synaptic vesicles the signal to release their neurotransmitter into the synaptic cleft. The Ca2+
ions bind with the cluster of proteins that docked the membrane of the synaptic vesicles with the active
zone. The binding of Ca2+ changes the shape of these proteins, making them move apart. As they move
apart a hole or pore appears in both the synaptic vesicle and the active zone it is attached to. Both membranes then form a fusion pore so the synaptic vesicles can release their contents into the synaptic cleft.
Another name for this process of fusion and release is exocytosis (Figure 6: Step 3).
The arrival of an action potential triggers the
release of neurotransmitters. How does it
trigger this release?
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The entry calcium ions into the presynaptic
terminal is another important step in the release of neurotransmitter. What happens after calcium levels rise?
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With synaptic vesicles fusing to the presynaptic membrane, how does the presynaptic
membrane not just continually increase in
size?
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LESSON READING
DEFINITIONS OF TERMS
Endocytosis – process by which
matter is taken in by a living cell
by invagination of its membrane to
form a vesicle.
Postsynaptic potentials – small
changes in voltage (membrane
potential) due to the binding of
neurotransmitter.
For a complete list of defined
terms, see the Glossary.
What happens to the membrane of the synaptic vesicles after they have broken open and released the
neurotransmitter they contain? If the open vesicles have not completely collapsed onto the presynaptic
membrane they can simply pinch off again and drift away to be filled once more with neurotransmitter.
This has been called ‘kiss and run’. Other times the fusion pore becomes so large that the vesicles seem
to flatten down and merge entirely with the presynaptic membrane. In these cases the little buds of the
presynaptic membrane pinch off back into the terminal, effectively creating new synaptic vesicles. Another
name for this process of pinching off and recovery is endocytosis.
Activation of receptors
How does the release of neurotransmitters from the presynaptic terminal into the synaptic cleft produce
an effect in the postsynaptic cell? The answer to this question begins with the binding of neurotransmitters to their receptors on the postsynaptic cell membrane (Figure 6: Step 4). Once this binding occurs,
the postsynaptic receptors too change their shapes, and in the process open ion channels located in the
postsynaptic membrane. These ion channels, which are called receptor-gated ion channels, because
they are activated by receptors, not by voltage, permit specific ions to pass into or out of the postsynaptic
cell (Figure 6: Step 5). Thus, the neurotransmitter in the synaptic cleft, by binding to receptors, allows
particular ions to pass through the postsynaptic cell’s membrane, changing the membrane potential at the
postsynaptic site and creating postsynaptic potentials.
Termination of synaptic transmission
Postsynaptic potentials are therefore brief changes in the postsynaptic membrane potential caused by the
activation of postsynaptic receptors by neurotransmitters. They are kept brief because the neurotransmitter is rapidly removed from the synaptic cleft, and once it is removed it can no longer activate its receptors.
Neurotransmitters can be removed by two mechanisms:
•
•
Wo r k b o o k
Lesson 3.2
Reuptake
Degradation by enzymes
Almost all central nervous system neurotransmitters are removed by reuptake (Figure 6: Step 6). This
simply involves taking the neurotransmitter back into the presynaptic terminal again, using a special energy-dependent pump called a transporter. This means that from the time that an action potential stimulates
release of neurotransmitter into the synaptic cleft, until the presynaptic terminal takes it back up again,
the postsynaptic receptors only have a brief exposure to the neurotransmitter. The process of reuptake
ensures that postsynaptic potentials are also quite brief.
The binding of neurotransmitters to receptors
causes ion channels to open, thus changing
the membrane potential in the postsynaptic
neuron. Can you predict how this change in
membrane potential might affect the postsynaptic neuron? What might result from this
change in membrane potential?
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Certain drugs inhibit the reuptake of neurotransmitter from the synaptic cleft. What
would happen if this reuptake was blocked?
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LESSON READING
Neurotransmitters can also be broken down in the synaptic cleft by enzymes. As far as we know only one
neurotransmitter is dealt with in this way, but it is an important one. Acetylcholine (ACh) is the neurotransmitter used at our neuromuscular junctions, where neurons instruct our muscles to contract. It is critical
that the postsynaptic potentials produced by ACh be short-lived because the quick breakdown of ACh is
important for us to have tight control over the timing of muscle contraction. So at the neuromuscular junction the synaptic cleft is awash with the specific enzyme that can chew up ACh, and stop it binding to its
receptor.
Summary
In conclusion remember that the communication between neurons requires several steps. First the presynaptic cell must fire an action potential. Once the action potential invades the presynaptic axon terminal,
the presynaptic cell releases neurotransmitters into the synaptic cleft. These neurotransmitters then cross
the synapse and bind to receptors on the postsynaptic cell. After binding to receptors, neurotransmitters
cause postsynaptic potentials in the postsynaptic cell.
Wo r k b o o k
Lesson 3.2
What do you predict would be the effect of
drugs or toxins that stop the breakdown of
ACh in the neuromuscular junction?
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83
STUDENT RESPONSES
On the diagram below, label and describe the steps of synaptic transmission.
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The goal of synaptic transmission is to send a signal from one neuron to another. Does it matter which ions channels open and
which ions flow into the postsynaptic cell? (Hint: Think about the effect positive and negative ions would have on the chances of
the postsynaptic neuron reaching threshold.)
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Wo r k b o o k
Lesson 3.2
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