Across the Gap: Synaptic Transmission

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Across the GapSynaptic Transmission
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• "You are your synapses. They are who you are."
• Joseph LeDoux, 2002 (in Synaptic Self)

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• 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)

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• 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.

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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

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• 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.

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• When an action potential reaches the axon
  terminal of a neuron, voltage-dependent calcium
  (Ca 2) channels embedded in the pre-synaptic
  membrane open and Ca 2 rushes in.
• The Ca 2 ions bind to the vesicles and cause
  the vesicles to move toward the membrane.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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 cells
  synapses.

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• 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.

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• 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

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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.

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• 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.

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•   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.

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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

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• 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.

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• 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

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• 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

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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.

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Dopamine

• 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.

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• Too little dopamine is associated with
  Parkinsons 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.

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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.

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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 Parkinsons
  disease are affected by this neurotransmitter.

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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.

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• 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."

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• endorphins are believed to produce four key
  effects on the body/mind
• 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.

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• 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.
  

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