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C 2.

2 Neural Signaling (AHL)


“How are electrical signals generated
and moved within neurons?”

“How can neurons interact with other cells?”


Learning Objectives
Include the action of voltage-gated sodium and potassium channels
Depolarization and repolarization during
C2.2.8 AHL and the need for a threshold potential to be reached for sodium
action potentials
channels to start to open.
Students should understand how diffusion of sodium ions both
Propagation of an action potential along a
C2.2.9 AHL inside and outside an axon can cause the threshold potential to be
nerve fibre/axon as a result of local currents
reached.
C2.2.10 Oscilloscope traces showing resting potentials
AHL and action potentials

Students should understand that ion pumps and channels are


C2.2.11 Saltatory conduction in myelinated fibres to
AHL achieve faster impulses clustered at nodes of Ranvier and that an action potential is
propagated from node to node.
Use neonicotinoids as an example of a pesticide that blocks
C2.2.12 Effects of exogenous chemicals on synaptic
AHL transmission (including cocaine) synaptic transmission, and cocaine as an example of a drug that
blocks reuptake of the neurotransmitter.
C2.2.13 Inhibitory neurotransmitters and generation Students should know that the postsynaptic membrane becomes
AHL of inhibitory postsynaptic potentials hyperpolarized.
Summation of the effects of excitatory and Multiple presynaptic neurons interact with all-or-nothing
C2.2.14
inhibitory neurotransmitters in a postsynaptic consequences in terms of postsynaptic depolarization.
AHL
neuron

Students should know that these nerve endings have channels for
positively charged ions, which open in response to a stimulus such
C2.2.15 Perception of pain by neurons with free nerve as high temperature, acid, or certain chemicals such as capsaicin in
AHL endings in the skin chilli peppers. Entry of positively charged ions causes the threshold
potential to be reached and nerve impulses then pass through the
neurons to the brain, where pain is perceived.
Consciousness as a property that emerges Emergent properties such as consciousness are another example of
C2.2.16
from the interaction of individual neurons in
Depolarization and repolarization during action potentials
Depolarization and repolarization during action potentials
A nerve impulse is a result of a change in
concentration of sodium (Na+) and
potassium (K+) ions along the cell membrane.
Depending on the
membrane potential
(voltage), we can distinguish
between a resting potential
and an action potential.
Resting potential: this is the potential
difference across a nerve cell membrane
when it is not stimulated. It is at
approximately -70mV.

Action potential: This is the reversal


(depolarisation) and restoration
(repolarisation) of the electrical
potential across a plasma membrane as
a nerve impulse passes along a neuron.
Depolarization and repolarization during action potentials

Due to an unequal distribution of


ions, and the abundance of negatively
charged proteins inside the axon
fibre, the membrane potential is
found to be at ca. -70mV during the
resting potential. An action potential
temporarily depolarizes the
membrane to a positive value.
Depolarization and repolarization during action potentials
Depolarization: The cell membrane's charge becomes positive to generate an
action potential. This is usually caused by positive sodium ions going into the cell.
Repolarization: The cell membrane's charge returns to negative after
depolarization. This is caused by positive potassium ions moving out of the cell.

http://faculty.southwest.tn.edu/rburkett/A&P1_m30.jpg
An Action potential is composed of two subsequent stages:
Depolarisation
http://upload.wikimedia.org/wikipedia/en/4/46/Ion_channel_activity_before_during_and_after_polarization.jpg

Depolarisation starts with an electrical stimulus being carried along the neuron fibre. This acts on
the voltage gated ion channels embedded within the membrane. The Na+ channel gates open,
allowing a flow of Na+ ions following the concentration gradient, into the interior of the cell. This
makes the membrane potential more positive inside compared to outside (ca. + 40 mV).

Repolarisation

The Na+ gated channels close again, and the voltage gated K+ channels now open, allowing a
K+ ions to diffuse out of the cell. This makes the inside of the cell more negative again. The
resting potential is going to be restored.
An Action potential is composed of two subsequent stages:
The action potential is initiated through the activation of voltage sensitive gates on ion
channels which open when a threshold voltage across the membrane is exceeded.

An action potential starts once the


At the resting potential the voltage
treshold potential of the axon
gated channel is closed. The flow of ions
membrane reaches -50 mV. This causes
can only occur through leak channels or
the voltage gated channels to open up,
the sodium potassium pump.
allowing Na+ ions to enter the cell.
Depolarization and repolarization during action potentials
An Action potential is composed of two subsequent stages:

https://youtu.be/oa6rvUJlg7o?t=439
Depolarization and repolarization during action potentials

https://phet.colorado.edu/sims/html/neuron/latest/neuron_all.html
Propagation of an action potential along a nerve fibre
A stimulus must be at or above a minimum intensity, known as the threshold of
stimulation to initiate an action potential. Either the depolarization is sufficient to fully
reverse the potential difference in the cytoplasm (from –70 mV to +40 mV), or it is not.
Propagation of an action potential along a nerve fibre
The movement of an impulse in form of an action potential along an axon is
due to the diffusion of sodium ions at the inside and outside of the axon fibre.
Sodium ions diffuse
Depolarization of this part of the
between different
axon is caused by the diffusion The movements of ions
concentrations inside
of Sodium ions into the axon. inside and outside the axons
and outside in
This reduces the concentration are called local currents.
opposite directions.
outside and increases it inside.
Propagation of an action potential along a nerve fibre

Local currents reduce the concentration gradient in the part of the neuron that has not yet
depolarized. This makes the membrane potential rise from -70 to -50mV. The Sodium channels
in the axon are voltage gated, which means they are triggered to open when the threshold
potential of -50 mV has been reached. Opening the Sodium channels causes depolarisation. The
local currents therefore cause a wave of depolarization followed by repolarization.
Oscilloscopes record the cell potential

http://cnx.org/resources/5c5f6a6365c3276619c4c3c7c3d2a91a/1220_Resting_Membrane_Potential.jpg

The cell potential (i.e. the voltage produced


by the movement of ions) can be measured
using microelectrodes impaled into cells. A
minimal amount of stimulus is needed to fire
an action potential (threshold minimum must
be reached). An oscilloscope image showing
the changes (in mV) can be obtained.
Oscilloscopes record the cell potential

The change in potential difference in the plasma membrane of a neurone


can be shown using an oscilloscope which traces the changes in voltage
over time. The action potential is transported along the axon fiber.
Annotate the diagram:
Oscilloscopes record the cell potential

https://www.mrgscience.com/topic-65-neurones-and-synapses.html
Saltatory conduction in myelinated axon fibres
What is the difference?

https://www.britannica.com/science/node-of-Ranvier
Saltatory conduction in myelinated axon fibres

https://jackwestin.com/resources/mcat-content/specialized-cell-nerve-cell/nodes-of-ranvier-propagation-of-nerve-impulse-along-axon-2
Ion pumps and channels are
clustered at the nodes of
Ranvier. An action potential is
therefore generated only at
these points, and from there
propagated in “jumps” from As a result of this, signal transduction
node to node. This is called occurs much faster (ca. 200m/s) than at
unmyleinated axon fibers (2m/s).
saltatory conduction.
Effects of exogenous chemicals on synaptic transmission

http://jungletaming.com/wp-content/uploads/2015/02/neo.png
Exogeneous chemicals are
substances which enter the body
from an outside source through
ingestion, inhalation or absorption
through the skin. The use of
neonicotinoids as pesticides has
resulted in effects on synaptic
transmission in honey-bees.

One of the most commonly


insecticides is imidacloprid, which is
often applied on crop fields in order
to fend off plant pests. The
increasing effects these insecticides
have on honey-bees have become
more and more of a concern.
http://www.willowoodusa.com/wp-content/uploads/2011/03/Imidacloprid-4SC-Box-and-Jug.jpg
https://oregonsustainablebeekeepers.files.wordpress.com/2013/03/bad.jpg
Effects of exogenous chemicals on synaptic transmission
Acetylcholine binds to acetylcholine
receptors. There are two types of
acetylcholine receptors (AChR) on the
postsynaptic membrane and transmit its
signal: muscarinic AChRs and nicotinic AChRs.

These receptors are


functionally different. The
muscarinic type mediates a
slow metabolic response, while
the nicotinic type mediate a
fast synaptic transmission of
the neurotransmitter.
Effects of exogenous chemicals on synaptic transmission
Neonicotinoids block Acetylcholine nicotine
receptors. Neonicotinoids are a class of neuro-active
insecticides chemically similar to nicotine and bind to
nicotinic acetylcholine receptors of a cholinergic
synapse in the CNS of insects and prevent the binding of
Acetylcholine. AChE cannot break down the pesticide.
Effects of exogenous chemicals on synaptic transmission
Neonicotinoids have mostly consequences for bees but are not toxic to
humans and other mammals. This is mostly because insects have a much
greater proportion of cholinergic synapses in the CNS, and the neonicotinoid
also binds much stronger to acetylcholine receptors in insects.

https://www.activistpost.com/wp-content/uploads/2013/06/bee__says_help1.jpg
In insects the
overstimulation at the
synapses results in
paralysis and death.

http://healingmanuka.com/wp-content/uploads/2017/10/planting-for-bees-001.png
Effects of exogenous chemicals on synaptic transmission

https://www.drugabus e.gov/sites /default/fil es/im ages /col orbox /cocrrenneuron.j pg


http://www.unity.nl/w ordpress/w p-content/uploads/2015/09/cocai ne-720x480.j pg

Effects on the synaptic transmission: Effects on the body:


• Cocaine acts at synapses that use dopamine • Dopamine is a pleasure NT
as a. neurotransmitter. • Causes enhanced feelings of pleasure and
• It blocks receptors on dopamine re-uptake euphoria
pumps, which therefore causes it to remain • Increases energy and alertness
in the synaptic cleft. • Highly addictive
• Therefore, dopamine builds up in the • Associated with depression (body reduces
synaptic gap. its own production of dopamine).
• Increases post-synaptic transmission and
continuous excitement.
Effects of exogenous chemicals on synaptic transmission
Look at the molecules below. Can you see any molecular similarities that
explain why all these structures can bind to acetylcholine receptors?
Inhibitory neurotransmitters
….and generation of inhibitory postsynaptic potentials
Pre-synaptic neurons can either excite or
https://www.lecturio.com/concepts/synapses-and-neurotransmission/

inhibit post-synaptic transmissions. This


depends on which neurotransmitter is
used, and which receptor they bind to.

Excitatory:
Neurotransmitters used:
Acetylchline
Glutamate
Acetycholine Dopamine
Glutamate
Dopamine
Consequence:
Increased influx of Na+ ions into postsynaptic
membrane, membrane more positive, easier
depolarization.

Inhibitory:
Neurotransmitters used:
GABA
Treshold Dopamine
Consequence:
Incresead influx of Cl- ions into postsynaptic
Treshold
membrane and hyperpolarization. Membrane is
more negative – more difficult to depolarize,
impuls inhibited.
Inhibitory neurotransmitters
Affected neurotransmitter systems
The following is a brief table of notable drugs and their primary neurotransmitter, receptor or method of action. It should be noted
that many drugs act on more than one transmitter or receptor in the brain

(Adrenaline)

http://jonlieffmd.com/wp-content/uploads/2013/05/neurotransmitters_table.jpg
Inhibitory neurotransmitters

http://beforeitsnew s.com/contributor/upload/30080/images/FiveLongTer mEffects


Alcohol (like THC or Benzodiazepenes) is an example of a sedetative
substance which affects the inhibitory neurotransmitters receptors.

Alcohol binds to glutamate receptors in the brain and enhances the inhibitory
effects of the neurotransmitter GABA which hyperpolarizes the postsynaptic
neurone. It also helps to increase the release of dopamine. Alcohol particularly
interacts with areas of the brain involved in decision making, memory formation
and impulse control. It impairs reaction times and muscle coordination.
Summation of the effects of excitatory and inhibitory
neurotransmitters in a postsynaptic neuron

Usually, postsynaptic neurons have many synaptic junctions with presynaptic ones. The
thing that decides if an impulse is passed on to create further neural activity is the
overall summation of excitatory and inhibitory input to the post synaptic membrane.
Summation of the effects of excitatory and inhibitory
neurotransmitters in a postsynaptic neuron
The effect of each input from a pre-
synaptic neuron is summative – and if
the summative effect reaches
threshold, an AP is propagated in the
axon of the post-synaptic neuron.

If the sum of the inhibitory and


excitatory signals are below the
threshold, the no action
potential will be triggered.
Summation of postsynaptic potentials
Analyze the oscilloscope graphs below and give reasons to decide
whether an action potential is successfully triggered or not.
Perception of pain by neurons with free nerve endings
in the skin
Pain receptors in the form of free nerve endings in the skin and other parts
of the body perceive stimuli such as a bee’s sting, heat or or puncturing of
the skin with a needle. The nerve endings are receptors of sensory neurons
and they are associated with channels for positively charged ions.
Perception of pain by neurons with free nerve endings
in the skin
When ion channels are activated and the
treshold potential is reached, a nerve impuls
is passed through the sensory neuron to the
spinal column and from there it is
transducted to the cerebral cortex in the
brain where pain is sensed and interpreted.
Perception of pain by neurons with free nerve endings
in the skin
Many different types of
stimuli can act on the
receptor channel
protein to cause positive
ions to move into the
axon and trigger an
action potential.

Out of a group of many membrane proteins, one


channel protein responds to both, temperature
and capsaicin (a chemical compound found in
chilli peppers).
Perception of pain by neurons with free nerve endings
in the skin

https://www.nbcnews.com/id/wbna4313263
Consciousness emerges from the interaction of
individual neurons in the brain

https://www.technologynetworks.com/neuroscience/news/new-theory-suggests-consciousness-is-the-brains-energy-field-341866
To be conscious of
something means to
be aware of it.

The exact way of how


consciousness is
generated is not
entirely clear yet.
However, it has been
agreed on that
consciousness emerges
from the interaction of
individual neurons in
the brain.
Consciousness emerges from the interaction of
individual neurons in the brain

Consciousness is an example of an emergent property. It is a


complex interaction between individual parts of the body.

https://en.wikipedia.org/wiki/Neural_correlates_of_consciousness#/media/File:Neural_Correlates_Of_Consciousness.jpg

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