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Transcript
Communication between Neurons
Properties of Synaptic Conduction
Temporal Summation:
Spatial Summation
Inhibitory Synapses
The Structures of the Synapse:
Vessicles
Pre-synaptic membrane
Post synaptic membrane
Sequence of chemical events at the synapse
Synthesis of neurotransmitters
Release of neurotransmitters
Action of neurotransmitters on Post Synaptic membrane
Reuptake or break down of neurotransmitters
Reading
Pinel, Biopsychology, Section 4.5-4.8
Or
Carlson Physiology of Behavior, Pages 42-52
Aims
To provide you with a list of the basic structures and chemicals
involved with information passing between neurones and to
describe the various steps involved. To point out how this process
differs from how the message travels along the neurone.
Objectives
By the end of this lecture you should be able to list the important
structures at the terminal button. You should also be able to
describe the stages of the process and how it differs from an
action potential.
How do we know this is different from communication within a nurone?
Initially we thought it was one long bit of neurone with all communication via
electrical action potentials and saltatory conduction, branching into spinal cord
(Whytte 1730)
Santiago Ramon y Cajal late 1800 studied slides of infant brains under the
microscope. He wanted to be an artist so he illustrated nerve cells and
demonstrated that neurones did not merge they were separated by a gap.
Charles Sherrington in 1906 called this gap a synapse and from his largely
behavioural studies was able to deduce most of the major properties of the
synapse. What Sherrington did was to very lightly pinch the paw of a dog and to
time how long before the dog would pull back his foot. He was basically looking
at the same type of reflex we’ve looked at before where you burn your finger
and withdraw your hand. He found this reflex withdrawal was happening too
slowly if this was all happening via action potentials. Eg speed of action
potential 40 m/s conduction through a reflex arc is 15m/s. delay must be
happening at synapse.
Properties of Synaptic Conduction
Sherington discovered 3 important properties of the synapse
i) Temporal Summation: He discovered if you pinched the dogs foot very very
lightly there was no response, if you did this 3 times in rapid succession the dog
would withdraw the foot. The more rapid each pinch followed on from the other
the more strong the response. Sherington surmised a single light pinch was too
light to set off an action potential in the next cell along but another pinch just
after the first would combine in some way with the first to set off the next cell.
John Eccles (1964) recorded activity in single neurones to show temporal
summation.
ii) Spatial Summation: same sort of thing except instead of doing ligth pinches in
the same place one after another, he did 3 light pinches simultaneously but in
different places on the dogs paw. the important thing about this is the next cell
along the arc is not just getting info from one cell but from lots of different cells.
Again one pinch from one cell was not enough to set off the action potential in
the next cell but one pinch coming from 3 different cells at the same time was
enough to set off the action potential. Again Eccles confirmed spatial
Summation.
iii) Inhibitory Synapses: When Sherrington pinched the dog vigorously the dog
apart from biting Sherington would not only contract its flexor muscle in its leg, it
would also relax its extensor muscle. Contraction of the extensor muscle moves
the paw away from the body while contraction of the flexor moves the paw
toward the body. So in order the paw is withdrawn after the pinch it has to excite
the contraction of the flexor muscle and inhibit contraction of the extensor
muscle. Again Eccles years later demonstrated the interneurone has an
exictatory synapse on the motor neurone of the flexor muscle and a inhibitory
synapse on the motor neurone to the extensor muscle.
Chemical communication at the synapse
One thing Sherington got wrong was he reckoned synaptic transmission was
still done by electricity. Otto Loewi (1920) showed this was not the case. He
stimulated the vagus nerve to a frogs heart which decreased the heart rate. He
then collected the liquid in the heart and transfered it to a second frogs heart
and saw a decrease in heart rate. He repeated the experiment only this time
stimulating the accelerator nerve to the heart, collecting the fluid and
transferring it to a second heart and this time observing an acceleration in heart
rate. Loewi reckoned however the nerves were affecting the heart it had to be
through chemicals rather than electricity.
Important Neurotransmitters
The chemicals taking the message from one nerve cell to the next are known as
neurotransmitters, below is a schematic diagram of the most important groups
of Neurotransmiters
Amino Acid Neurotransmitters
Glutamate- excitatory
GABA (gamma-aminobutyric acid)- inhibitory allow Cl- ions into membrane
The neurotransmitters in the vast majority of fast acting,. Directed synapses in
the CNS.
Monamines
Single amino acid
Catecholamines- dopamine, norepinephrine, epinephrine (noradrenaline and
adrenaline)
Dopamine involved with reward centres in the brain
Norepinephrine parasmypathetic ns
Epinephrine smypathetic ns
Indolamines- serotonin
Serotonin – mood drugs affecting serotonin include prozac
Acetylecholine – efferent neurones at muscle synapses
Peptide – endorphins involved with pain centres, naturally occurring
analgesics, non natural morphine
Soluble Gasses
The Structures of the Synapse
At the end of the axon is the terminal button, contained within the button is
mitochondia, concerned as they are in the cell body of the neurone with
breakdown of nutrients to provide energy, their presence indicates synaptic
communication is costly in terms of energy. Golgi bodies involved here with
packaging up the neurotransmitters as vesicles (small bladders) and
microtubules which are involved in transport of certain types of
neurotransmitters synthesised by the ribosomes in the cell body of the axon.
There many different types of neurotransmitters and we will be looking at these
and their different functions in more detail in next weeks lecture. The flat area of
the terminal button is known as the pre-synaptic membrane, the corresponding
membrane on the dendrite of the adjacent neurone is known as the postsynaptic membrane and between the two is known as the synaptic cleft. The
majority of axons terminate at the dendrite of the adjacent cell, more precisely
at dendritic spurs - small synaptic buds covering the surface of many dendritesand are known as axodendritic synapses. However there are Axosomatic
synapses, located between the axon and cell body, and Axoaxonal synapses,
between two axons of adjacent cells and even dendrodendritic synapses
between the dendrites of two neurones capable of transferring information in
either direction. The different functions of these different types of synapses will
be explained later in terms of neural integration.
The sequence of chemical events at the synapse
i)Synthesis of neurotransmitters
As I said earlier cetrain neurotransmitters are made in the cell body or soma of
the neurone. These are called Peptides and are made from chains of amino
acids are basically short proteins. They are packaged up in vesicles by the
Golgi bodies and sent along the axons down the microtubules at the hair raising
speeds of between 1 -100mm per day. The majority of neurotransmitters are
synthesised in the cytoplasm of the terminal button and from products obtained
the diet. Acetylcholine for instance, a common neurotransmitter, is synthesised
from choline which abundant in cauliflower, so now you know what to eat before
the exams. These smaller transmitters are also packed in vesicles and found
with the others around the pre-synaptic membrane.
ii) Release of neurotransmitters
The release of neurotransmitters is triggered by the arrival at the terminal button
of an action potential along the axon. Voltage sensitive Ca ion gates in the presynaptic membrane are opened. When the Calcium ions enter the terminal
button the vesicles fuse with the pre-synaptic membrane. The Calcium is
believed to be important in the process, following fusion of the vesicles to the
membrane, of breaking the vesicle apart and releasing the neurotransmitters
into the synaptic cleft. When the vesicle joins with the pre-synaptic membrane it
increases the size of the membrane slightly. Obviously if this went on
indefinitely you’d have huge terminal buttons, so what happens is at the tip of
the button where it meets the axon, some membrane breaks off into the
cytoplasm and migrates to the golgi body where it is recycled into more vesicles
for neurotransmitters.
iii) Action of neurotransmitters on Post Synaptic membrane
The neurotransmitter diffuses across the synaptic cleft until it binds with a
specific receptor on the post-synaptic membrane. There are two types of
receptors a) Ion channel linked receptors and b) G-Protein linked receptors.
Once the neurotransmitter binds to an ion-channel receptor, the ion channel will
open allowing ions to flow into the membrane. If the ion channel allows Na,
sodium in then providing enough channels are open and enough Sodium flows
in then the voltage of the cell is made less negative and an action potential is
set off running down the axon, such a potential is known as an Excitatory Post
Synaptic Potential (EPSP). If on the other hand the channel allows Potassium
ions out then the voltage is made more negative making it more difficult for a
subsequent action potential to start. This is known as an Inhibitory Post
Synaptic Potential (IPSP).
The second type of receptor is a G-Protein linked receptor and requires the cell
to be expend energy so are also called metabotropic receptors. Binding to one
of these receptors results in a sub-unit of the protein breaking away which either
directly opens an ion gate or it activates an enzyme in the cell membrane which
synthesises a second messenger. Once created the second messenger does
one of three things opens an ion channel, directly influences the metabolic rate
of the cell or enters the cell nucleus, binds with the DNA thereby influencing the
genetic material of the cell. Usually Peptide neurotransmitters are involved with
these long lasting changes in cell activity, the other smaller neurotransmitters
being only involved with rapid production of EPSP’s or IPSP’s.
iv) Reuptake or break down of neurotransmitters
The neurotransmitters do not stay attached to the receptors forever, if they did
there would be no point in sending any more messages as the postsynaptic
potential would be continually firing anyway. There are two ways the
neurotransmitters are removed from the receptor, either it is broken down by an
enzyme, eg acetylecholine is broken down by acetylcholinesterase, or it is
reabsorbed whole by the pre-synaptic membrane, repackaged in vesicles and
eventually to be released back into the synaptic cleft when the next Action
potential shows up.