Download LESSON 3.3 WORKBOOK

LESSON 3.3 WORKBOOK
Why does applying pressure relieve
pain?
DEFINITIONS OF TERMS
Postsynaptic potentials – small
changes in voltage (membrane
potential) due to the binding of
neurotransmitter.
Receptor-gated ion channels
– ion channels that open or close
in response to the binding of a
neurotransmitter.
For a complete list of defined
terms, see the Glossary.
In the last lesson, we learned how neurons send signals
across the synaptic cleft via synaptic transmission. But two
questions remain — how does this type of signaling result
in an action potential in the postsynaptic cell? And thinking back to our pain framework, how does communication
between neurons in the pain pathway allow us to control
how we perceive painful stimuli? The answer to both questions lies in the specialized structure at the start of the axon
where the action potential originates — the axon hillock.
Postsynaptic potentials
Remember that the local changes in membrane potential created by neurotransmitters binding to their
receptors at the synaptic cleft are referred to as postsynaptic potentials. Interestingly, the kind of
postsynaptic potential a particular synapse produces does not depend on the neurotransmitter itself.
Instead, it is determined by the characteristics of the postsynaptic receptors the neurotransmitter binds
to – in particular, by the specific type of ion channel they open. Receptor-gated ion channels in the
postsynaptic membrane are much more versatile than the voltage-gated ion channels in the axon. First,
the postsynaptic membrane contains more than just Na+ and K+ channels. The postsynaptic membrane
contains anion channels (permeable to negatively charged ions) as well as other cation channels (permeable to positively charged ions). Second, receptor-gated ion channels can move ions out of the postsynaptic cell as well as into it. This means that the receptor-gated ion channels can have a varied range
of effects on the postsynaptic cell, as we shall see. The end goal of all these effects is on the threshold
that regulates whether an action potential will fire.
We can identify two major types of receptor-gated ion channels in the postsynaptic membrane: cation
channels (permeable to positively charged ions) and anion channels (permeable to negatively charged
ions):
Wo r k b o o k
Lesson 3.3
Two cation channels permeable to:
Sodium (Na+)
Calcium (Ca2+)
One anion channel permeable to:
Chloride (Cl-)
What causes receptor-gated ion channels to
open? How is that different from the voltagegated channels we saw in the axon?
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Why does opening sodium or calcium ion
channels cause a neuron to depolarize?
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Why does opening chloride ion channels
cause a neuron to hyperpolarize?
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LESSON READING
DEFINITIONS OF TERMS
Excitatory postsynaptic
potentials (EPSP) – graded
postsynaptic depolarizations,
which increase the likelihood
that an action potential will be
generated.
Inhibitory postsynaptic
potentials (IPSP) – graded
postsynaptic hyperpolarizations,
which decrease the likelihood
that an action potential will be
generated.
Integration – adding or
combining a number of individual
signals into one overall signal.
For a complete list of defined
terms, see the Glossary.
Note that these channels are different from the voltage-gated sodium and calcium channels we talked
about on the axon and the presynaptic terminal because they are stimulated to open by a neurotransmitter binding to its receptor, and not by a change in voltage. When channels open that are permeable to
either sodium or calcium, Na+ or Ca2+ ions can enter the cell, as we saw before. This entry of positive
ions depolarizes the postsynaptic membrane, making the membrane potential more positive, or phrased
another way, less negative. This is called an excitatory postsynaptic potential (EPSP) and it brings the
postsynaptic cell closer to the threshold for firing an action potential. However, when channels that are
permeable to chloride (Cl-) open, the negatively charged Cl- ions that are in high concentration outside the
cell, are pushed inside by the force of diffusion. This entry of negative ions hyperpolarizes the postsynaptic
membrane, making the membrane potential more negative. This is called an inhibitory postsynaptic potential (IPSP) and it brings the postsynaptic cell farther away from the threshold to fire an action potential.
Threshold – Voltage at which Na+ channels open Inhibitory Postsynap/c poten/als (IPSP) caused either by entry of Cl-­‐ ions, or exit of K+ ions Excitatory Postsynap/c poten/als (EPSP) caused by entry of either Na+ or Ca2+ ions Figure 7: Getting to threshold. IPSPs decrease the chance of
reaching threshold because they make the membrane potential
more negative. EPSPs increase the chance of reaching threshold because they make the membrane potential more positive.
Recall that an action potential is only
initiated after the threshold that opens
the axon’s voltage-gated Na+ channels
is reached. Because EPSPs depolarize the postsynaptic membrane, they
bring the membrane potential closer
to threshold, increasing the likelihood
that the voltage-gated Na+ channels
will open and the postsynaptic neuron
will fire an action potential. Conversely
because IPSPs hyperpolarize the
postsynaptic membrane they move
the membrane potential further away
from threshold, decreasing the likelihood the voltage-gated Na+ channels
will open and the postsynaptic neuron
will fire an action potential. (Figure 7).
Remember though that a single dendritic tree may have hundreds of thousands of synapses, all of which
receive inputs from presynaptic terminals. What happens when an EPSP and an IPSP arrive at the same
time close to each other? Do they simply cancel each other out in the membrane? Obviously this isn’t a
good solution and each neuron has the job of integrating all these many different types of inputs into a
coherent output. They do this through the process of integration.
Wo r k b o o k
Lesson 3.3
Why do EPSPs increase the likelihood of firing an action potential?
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Why do IPSPs decrease the likelihood of firing an action potential?
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LESSON READING
Excitatory Synapse: Neurotransmi4ers open Na+ or Ca2+ channels producing EPSPs. Inhibitory Synapse: Neurotransmi4ers open either K+ or Cl-­‐ channels producing IPSPs. DEFINITIONS OF TERMS
Axon hillock – specialized part of
a neuron‘s cell body that connects
to the axon. As a result, the initial
segment or axon hillock is the site
where action potentials originate.
Axon hillock reaches threshold and acDon potenDal is fired. IPSPs encounter EPSPs. Threshold is not reached and no acDon potenDal is fired. Figure 8: Axon hillock. The axon hillock generates an action potential if the excitatory inputs
reach threshold to open the voltage-gated Na+ channels. The axon hillock will not generate
an action potential if the inputs do not reach the threshold to open the voltage-gated Na+
channels.
For a complete list of defined
terms, see the Glossary.
The integration of all local postsynaptic potentials (EPSPs and IPSPs) occurs in the axon hillock (Figure
8). The goal of input integration is to put the neuron into a final electrical state whereby it can either fire an
action potential or not.
Generally:
•
The axon will only fire an action potential if the postsynaptic membrane reaches the threshold to
open the axon’s voltage-gated Na+ channels. This can only happen when the excitatory inputs
are greater than the inhibitory inputs.
•
The axon will not fire an action potential if the postsynaptic membrane does not reach the
threshold to open the axon’s voltage-gated Na+ channels. This happens when the excitatory inputs aren’t great enough, and/or when the inhibitory inputs are greater than the excitatory inputs.
The process of synaptic integration is in continuous operation in every neuron in the nervous system. Each
cell integrates all of the synaptic information it receives at any one time, and depending on the balance of
excitation and inhibition, it either fires an action potential or it doesn’t.
Wo r k b o o k
Lesson 3.3
To further explore this idea let’s examine how applying pressure can relieve pain, but before we dive into
that discussion, let’s first remind ourselves of the pathway to get pain to the brain.
Under what circumstances will the axon hillock initiate an action potential? Under what
circumstances will the axon hillock not initiate an action potential? Why?
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LESSON READING
The pain synapse in the spinal cord
Recall that the pain pathway has four neurons. The first is in the periphery, the second is in the spinal cord,
the third is in the thalamus, and the fourth is in the somatosensory cortex. Let’s take a closer look at the
synapse between the first neuron and the
second in the spinal cord.
DEFINITIONS OF TERMS
Projection neuron – neuron
whose axons make synapses in
the brain.
For a complete list of defined
terms, see the Glossary.
In the spinal cord, neurons carrying pain
stimuli make synaptic connections within
the grey matter in the area that deals with
sensory information called the dorsal horn.
Specifically, the first pain neurons connect
to projection neurons that then project up
the spinal cord, carrying pain information to
the third neuron in the thalamus (Figure 9).
But the first pain neurons aren’t the only
neurons that make connections with the
projection neurons. A different type of neuron that is sensitive to pressure, not to pain,
also connects with the same projection
neuron (Figure 9). We call these connections between pain, pressure and projection neurons a circuit. This circuit is the first
way we manage our responses to painful
stimuli. We can diagram how the circuit is
wired (Figure 10).
Figure 9: Pain and pressure synapse in
the spinal cord. Neurons carrying painful
information, as well as neurons carrying pressure information both synapse on the same
projection neuron that carries information to
the brain.
Pain neuron Projec-on neuron Interneuron To Brain Pressure neuron Figure 10: Wiring of pain and pressure synapse in
the spinal cord.
How the circuit works
Now that we know how the circuit is “wired”, let’s look at how it works.
Wo r k b o o k
Lesson 3.3
Remember, that the neurons carrying painful stimuli synapse on the projection neurons. These pain neurons make excitatory synapses with projection neurons. This means that when pain neurons are activated
by painful stimuli they will always excite the projection neurons to produce an action potential.
What is the benefit of having both pain and
pressure sensitive neurons synapsing on the
same projection neuron?
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How does applying pressure relieve some of
our pain?
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LESSON READING
However, remember that the projection neurons are also connected to pressure sensitive neurons. But
these neurons make inhibitory synapses with the projection neurons. This means that when pressuresensitive neurons are activated by pressure stimuli, they will always inhibit the projection neurons, preventing them from producing an action potential.
DEFINITIONS OF TERMS
Behavioral inhibition –
inhibition of behavior.
Neural inhibition – inhibition of
neural signaling.
For a complete list of defined
terms, see the Glossary.
We can see this circuit in action when we bang our elbow or stub our toe, and then immediately go to rub
it. By rubbing the painful area we’re applying pressure that will activate our pressure-sensitive neurons.
These neurons will then communicate with the projection neurons in the spinal cord and inhibit them so
they’ll no longer tell the brain that they’re getting painful information from the first pain neurons. It’s all a
matter of balancing excitatory and inhibitory inputs. It’s not quite the same as “No brain, no pain”, but if the
pain never gets to the brain, we certainly can’t feel it.
Excitation vs Inhibition – It’s just a bit more complicated
Note that an inhibitory postsynaptic potential, which leads to neural inhibition, does not always produce
behavioral inhibition. For example, suppose a group of neurons actually prevents a particular movement from taking place, for instance if they hold your head erect, preventing it from falling forward. If these
neurons experience enough IPSPs they won’t fire an action potential and will experience neural inhibition.
But what effect will this have on your head? In fact if these neurons are inhibited, i.e. prevented from functioning, they will no longer be able to prevent your head falling onto your chest. Thus, inhibiting inhibitory
neurons makes the behavior more likely to occur.
If we think about neural excitation we can see that the same thing occurs: If we activate neurons that
inhibit a behavior, we will tend to suppress that behavior. For example, when we are dreaming, a particular
set of inhibitory neurons in the brains becomes active and prevents us from getting up and acting out our
dreams.
It is important to remember that all neurons need to reach threshold before they can fire an action potential
and communicate with other neurons via synaptic transmission. Whether they will reach that threshold
depends on how the axon hillock integrates the hundreds of thousands of excitatory and inhibitory inputs
that fall onto the dendritic tree. If the action potential is fired, whether that neuron will have an excitatory or
inhibitory effect on the postsynaptic cells it communicates with will depend on which neurotransmitters it
releases, how they interact with their receptors on the postsynaptic side and which ion channels they open.
In summary, an action potential always precedes synaptic transmission, and an action
potential is always preceded by reaching threshold, and to reach threshold more excitatory
inputs than inhibitory inputs are required (even if the neuron is inhibitory).
Wo r k b o o k
Lesson 3.3
Can you predict the effects of damage to
our neurons that prevent us acting out our
dreams?
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STUDENT RESPONSES
What must always precede the release of neurotransmitter?
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What must always precede the firing of an action potential?
Remember to identify your
sources
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Therefore, even in the case of an inhibitory neuron, what sequence of events must occur before it can release neurotransmitter
to inhibit the postsynaptic cell?
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Wo r k b o o k
Lesson 3.3
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