Transcript Across the Gap

Across the Gap:
Synaptic Transmission
"You are your synapses. They
are who you are."
Joseph LeDoux, 2002 (in Synaptic Self)
• Communication of information between neurons
is accomplished by movement of chemicals across
a small gap called the synaptic cleft.
• When the Action Potential reaches the axon
terminal,chemicals, called neurotransmitters, are
released from the neuron at the presynaptic nerve
terminal. (Axon)
• The neurotransmitters then cross the synaptic cleft
and are accepted by the post-synaptic neuron at
specialized sites called receptors. (Dendrite)
• The action that follows activation of a
receptor site may be either depolarization
(an excitatory postsynaptic potential) or
hyperpolarization (an inhibitory
postsynaptic potential).
• A depolarization makes it MORE likely
that an action potential will fire; a
hyperpolarization makes it LESS likely that
an action potential will fire.
Synaptic Transmission
• Neurotransmitters: are chemicals produced by
the neuron and packaged into vesicles at axon
terminals.
• At rest, neurotransmitter-containing vesicles
are stored at the axon terminals of the neuron
• A small number of vesicles are positioned
along the pre-synaptic membrane in places
called "active zones.“
• Other vesicles are held close to these zones,
but further from the membrane itself until
they are needed.
• The vesicles are held in place by Ca 2+sensitive vesicle membrane proteins
(VAMPs), which bind to actin filaments,
microtubules, and other elements of the
cytoskeleton.
– When an action potential reaches the axon
terminal of a neuron, voltage-dependent
calcium (Ca 2+) channels embedded in the presynaptic membrane open and Ca 2+ rushes in.
– The Ca 2+ ions bind to the vesicles and cause
the vesicles to move toward the membrane.
• Fusion then takes place: the vesicle membrane and
the pre-synaptic membrane connect to form a
small pore.
• This pore grows larger and larger until the vesicle
releases its contents into the synaptic cleft
(exocytosis).
• Following exocytosis, the vesicular membrane
forms a pit and pinches off to form a new vacant
vesicle.
• This vesicle is then either refilled with more of the
neurotransmitter, or sent to the cell body where it
is processed into a new vesicle.
• The neurotransmitters diffuse across the
synaptic cleft and bind to receptors on the
post-synaptic membrane.
• This causes ionic channels to open.
• Some neurotransmitters cause Na+ channels
to open, allowing the influx of Na+ ions
into the neuron and generating a new action
potential.These are excitory
neurotransmitters.
• Some neurotransmitters open Cl- channels.
This allows the influx of Cl- ions into the
neuron and make the inside even more
negative.
• In this case, an action potential will NOT be
produced. Neurotransmitters that act in this
way are said to be inhibitory.
• After a neurotransmitter molecule has been
recognized by a post-synaptic receptor, it is
released back into the synaptic cleft.
• It must be quickly removed or chemically
inactivated in order to prevent constant
stimulation of the post-synaptic cell and an
excessive firing of action potentials.
• Some neurotransmitters are removed from
the synaptic cleft by special transporter
proteins on the pre-synaptic membrane.
• These transporter proteins carry the
neurotransmitter back into the pre-synaptic
cell, where it is either re-packaged into a
vesicle or broken down by enzymes.
• This is called reuptake.
• Other neurotransmitters merely quickly
diffuse away from the receptors into the
surrounding medium.
• One important neurotransmitter,
acetylcholine, has a specialized enzyme for
inactivation right in the synaptic cleft.
• Acetylcholinesterase is an enzyme which
serves to inactivate acetylcholine by
hydrolysis.
SUMMATION:
• One neuron can have thousands of
synapses on its body and dendrons.
• So it has many inputs, but only one
output. The output through the axon is
called the Grand Postsynaptic
Potential (GPP)
• The GPP is the sum of all the excitatory
and inhibitory potentials from all that
cell’s synapses.
• If there are more excitatory potentials than
inhibitory ones then there will be a GPP, and
the neuron will “fire”, but if there are more
inhibitory potentials than excitatory ones then
there will not be a GPP and the neuron will
not fire.
• This summation is
the basis of the
processing power in
the nervous system.
• A nervous
system,including a
human brain, is
made by connecting
enough neurons
together
WHY THE GAPS?
• 1. They make sure that the flow of
impulses is in one direction only. This is
because the vesicles containing the
transmitter are only in the presynaptic
membrane and the receptor molecules
are only on the postsynaptic membrane.
• 2. They allow integration. An impulse traveling
down a neuron may reach a synapse which has
several post synaptic neurons, all going to different
locations. The impulse can thus be dispersed. This
can also work in reverse, where several impulses can
converge at a synapse.
• 3. They allow ‘summation’ to occur. Summation
allows for ‘grading’ of nervous response – if the
stimulation affects too few presynaptic neurons or
the frequency of stimulation is too low, the impulse
is not transmitted across the cleft.
4. They allow the ‘filtering out’ of continual
unnecessary or unimportant background
stimuli. If a neuron is constantly stimulated
(e.g. clothes touching the skin) the synapse
will not be able to renew its supply of
transmitter fast enough to continue passing the
impulse across the cleft. This ‘fatigue’ places
an upper limit on the frequency of
depolarization.
Neurotransmitters
– Chemicals that are produced within a
neuron, are released by a stimulated
neuron, and cause an effect on adjoining
neurons.
– There are two types of neurotransmitters:
1. Small molecule neurotransmitters:
2. Neuropeptides
1. Small molecule neurotransmitters:
-synthesized locally within the axon
terminal, usually by enzyme action.
-They are released in a pulse into
synaptic cleft every time an action
potential reaches an axon terminal.
Their effect is point-to- point and
short in duration.
2.Neuropeptides:
-synthesized by transcription and
translation of gene sequence. ER and
Golgi Apparatus are involved in
packaging.
-are released gradually in response to
general increases in neuron firing;
-their effects are usually widespread
because they are often released into
extracellular fluid or the bloodstream
• it was initially assumed that there is only one kind
of receptor for each neurotransmitter;
• research has shown that each neurotransmitter
binds to more than one type of receptor
• receptor subtypes are located in different brain
areas
• this allows the same neurotransmitter to signal
differently at various locations; postsynaptic
neurons are influenced in different ways based on
the type of receptor
Acetylcholine
• Acetylcholine (Ach) is an example of a
small molecule neurotransmitter. It is an
excitatory neurotransmitter
• The synthesis of ACh requires the enzyme
choline acetyltransferase
• It is found at various locations throughout
the central and peripheral nervous systems
and at all neuromuscular junctions.
Dopamine
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Dopamine & epinephrine are primarily inhibitory
neurotransmitters that produce arousal.
the most likely explanation for this effect is that
the postsynaptic cells for these neurotransmitters
are themselves inhibitory.
There are 3-4 times more cells that respond to
dopamine in the CNS than cells that respond to
epinephrine.
Dopamine affects a wide variety of brain
processes, many of which are involved in the
control of movement, the formation of emotional
responses, and the perception of pain and
pleasure.
• Too little dopamine is associated with
Parkinson’s disease.
• Too much dopamine is associated with
schizophrenia
• Dopamine is also associated with addiction
to cocaine, alcohol, and other drugs
• It may also play an important role in
obesity. According to a study, obese people
have fewer receptors for dopamine.
Serotonin
• Within the brain, serotonin is associated with a
variety of important centers, including those that
control appetite, memory, sleep, and learning.
• Serotonin is also closely associated with feelings
of well being, acting in conjunction with
endorphins, GABA, and dopamine to generate the
biological process known as the reward cascade.
• Many pharmaceuticals designed to fight
depression, bipolar disorder, and a number of
other mood-related conditions function by
stimulating serotonin production or inhibiting its
uptake.
GABA
• GABA or gamma-aminobutyric acid is the most
important and widespread inhibitory
neurotransmitter in the brain.
• Excitation in the brain must be balanced with
inhibition. Too much excitation can lead to
restlessness, irritability, insomnia, and even
seizures.
• GABA is able to induce relaxation, analgesia, and
sleep. Barbiturates are known to stimulate GABA
receptors, and hence induce relaxation.
• Several neurological disorders, such as epilepsy,
sleep disorders, and Parkinson’s disease are
affected by this neurotransmitter.
Endorphins
• endorphins ("endogenous morphine") are one of
several morphine-like substances (opioids) that
occur within our brains. Their molecular structure
is very similar to morphine but with different
chemical properties.
• Endorphins are polypeptides containing 30 amino
acid units. They are manufactured by the body to
reduce stress and relieve pain.
• Usually produced during periods of extreme
stress, endorphins naturally block pain signals
produced by the nervous system.
• The human body produces at least 20
different endorphins
• Beta- endorphin appears to be the endorphin
that seems to have the strongest affect on
the brain and body during exercise.
• Prolonged, continuous exercise like
running, long-distance swimming, aerobics,
cycling or cross-country skiing appears to
contribute to an increased production and
release of endorphins. This results in a sense
of euphoria that has been popularly labeled
the "runner's high."
• endorphins are believed to produce four key
effects on the body/mind:
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they enhance the immune system,
they relieve pain,
they reduce stress,
they postpone the aging process.
Scientists also have found that beta-endorphins
can activate human NK (Natural Killer) cells
and boost the immune system against diseases
and kill cancer cells.
• Chocolate is by far the most popular endorphin-producing
food on Earth.
• In addition to sugar, caffeine and fat, chocolate contains
more than 300 different constituent compounds, including
anandamide, a chemical that mimics marijuana's soothing
effects on the brain.
• It also contains chemical compounds such as flavanoids
(which are also found in wine) that have antioxident
properties and reduce serum cholesterol.
• Although the combined psychochemical effects of these
compounds on the central nervous system are poorly
understood, the production of endorphins are believed to
contribute to the renowned "inner glow" experienced by
dedicated chocolate lovers.