Synaptic Transmission

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Synaptic Transmission

• Synapse specialized junction where an axon
  terminal contacts another neuron or cell type
• Types of synapses
• Electrical synapses
• Chemical synapses
• An understanding of synaptic transmission is
  necessary to understand the operations of the
  nervous system (ie. actions of psychoactive
  drugs, causes of mental disorders, neural basis
  of learning and memory)

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Electrical Synapses

• Allows the direct transfer of ionic current from
  one cell to the next.
• Gap Junction is composed of 6 connexins that
  make up a connexon. (Pore size 2nm)
• Ions can flow bidirectionally.
• Cells are electronically coupled.
• Conduction speed is very fast.
• Found in neuronal pathways associated with
  escape reflexes or in neurons that need to be
  synchronized.
• Common in non neuronal cells.
• Important in development

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Chemical Synapses

• Synaptic cleft
• 20 50 nm wide
• Held together by a fibrous extracellular matrix
• Synaptic bouton (presynaptic element)
• Contains synaptic vesicles (50nm in diameter)
  and secretory granules (100 nm) called large,
  dense core vesicles.
• Membrane differentiations accumulations of
  proteins on either side of the synaptic cleft
• Active zones presynaptic site of
  neurotransmitter release
• Postsynaptic density contains receptors to
  translate intercellular signal (neurotranmitter)
  into an intracellular signal (chemical change or
  membrane potential change)

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Synapses can be categorized by

• Connectivity which part of the neuron is
  postsynaptic to the axon terminal
• Synapse anatomy
• Size and shape
• Appearance of the pre and postsynaptic membrane
  differentiations.
• Grays type I synapses asymmetrical
  (postsynaptic membrane is thick)
• Grays type II synapses - symmetrical

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CNS Synapses types of connections
Axodendritic
Axosomatic
Axoaxonic
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Synapses differentiated by size and shape.
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Categories of CNS membrane differentiations.
Grays type I synapses
Grays type II synapses
Usually Excitatory
Usually Inhibitory
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• Synaptic Junctions Exist Outside the Brain

• Junctions between autonomic neurons and glands,
  smooth muscle, and heart.
• The Neuromuscular Junction
• Transmission is fast and reliable due to large
  size with many active zones and a motor end plate
  with specialized folds for more receptors.

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Requirements of Chemical Synaptic Transmission.

• Mechanism for synthesizing and packing
  neurotransmitter into vesicles.
• Mechanism for causing vesicle to spill contents
  into synaptic cleft in response to action
  potential.
• Mechanism for producing an electrical or
  biochemical response to neurotransmitter in
  postsynaptic neuron.
• Mechanism for removing transmitter from synaptic
  cleft.
• Must be carried out very rapidly.

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Neurotransmitters

• Amino Acids
• synaptic vessicles
• Amines
• synaptic vessicles
• Peptides
• secretory granules.
• Peptides may exist in the same axon terminals as
  amino acids and amines.
• Fast transmission uses Amino acids or ACh.
• Slow transmission may use any of the three types
  of neurotransmitters

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Neurotransmitter Synthesis and Storage
Synthesis of peptide neurotransmitters
Synthesis of amine and amino acids
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Neurotransmitter Release

• Action potential enters the axon terminal.
• Voltage gated Ca channels open.
• Ca activates proteins in the vesicle and active
  zone.
• Activated proteins causes synaptic vesicles to
  fuse with membrane.
• Neurotransmitter is released via exocytosis.
• Note Peptide release requires high frequency
  action potentials and is slower (50 msec vs. 0.2
  msec).

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Neurotransmitter Receptors and Effectors

• Neurotransmitters must bind to specific receptor
  proteins in the postsynaptic membrane.
• Binding causes a conformational change in the
  receptor.
• A change in structure equals a change in
  function.
• Over 100 different types of receptors.
• Two major categories of receptors
• Transmitter (ligand) gated ion channels.
• G-protein coupled receptors.

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Ligand-gated Ion Channels

• Structure Channel protein with a ligand binding
  domain.
• Neurotransmitter binding causes channel to open.
• Consequence depends on the specific ions that
  pass through the pore.
• Na and K channels cause depolarization and are
  excitatory.
• Cl- channels cause hyperpolarization and are
  inhibitory.
• Activation is generally rapid and is mediated by
  amino acids and amines.

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Excitatory Postsynaptic Potential (EPSP)
Excitatory Neurotransmitters ACh and glutamate
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Inhibitory Postsynaptic Potential (IPSP)
Inhibitory Neurotransmitters Glycine and GABA
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G Protein-Coupled Receptors

• Structure Receptor protein with a ligand binding
  domain and connected to G protein consisting of
  an alpha, beta and gama subunit.
• Activation 1) Ligand binds to receptor 2)
  Receptor activates G-protein 3) G-protein
  dissociated 4) alpha subunit activates an
  effector protein.
• Effectors G-proteins act in one of two ways
• By opening ion channels
• By activating enzymes that synthesize
  second-messenger molecules.
• Tend to be slower, longer lasting and have
  greater diversity than ligand gated ion channels.
• Ligand may bind to a family of receptors with
  different effects due to specific receptor type.

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Autoreceptors and Presynaptic Inhibition

• Receptors are sometimes found on the presynaptic
  terminal.
• Activation leads to
• Inhibition of neurotransmitter release
• Neurotransmitter synthesis.
• Autoreceptors may act as a brake on the release
  of neurotransmitters.

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Neurotransmitter Recovery and Degradation

• Neurotransmitters must be cleared from the
  synapse to permit another round of synaptic
  transmission.
• Methods
• Diffusion
• Enzymatic degradation in the synapse.
• Presynaptic reuptake followed by degradation or
  recycling.
• Uptake by glia
• Uptake by the postsynaptic neuron and
  desensitization.

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Neuropharmacology

• Synaptic transmission is a chemical process and
  therefore can be affected by drugs and toxins.
• Neuropharmacology is the study of the effects of
  drugs on the nervous system
• Receptor Antagonists inhibit the normal action
  of a neurotransmitter.
• Curare blocks the action of ACh at the
  neuromuscular junction.
• Receptor Agonists mimic the action of a
  neurotransmitter.
• Morphine activates Mu-opiate receptors in the
  brain.
• Nervous system malfunctions are often related to
  neurotransmission errors.

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Synaptic Integration

• Each neuron may receive thousands of inputs in
  the form of ion channel and G-coupled protein
  activation.
• These complex inputs give rise to simple output
  in the form of action potentials.
• Neural computation
• Neurotransmitters are released in quanta.
• EPSP Summation
• Neurons do sophisticated computations by adding
  together EPSPs to produce a significant
  postsynaptic depolarization.
• Types of Summation Spatial and Temporal
  Summation.

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Dendritic Cable Properties
-Triggering of an action potential depends on how
far the synapse is from the spike initiation zone
and the properties of the dendrite (ie. Internal
and membrane resistance.) -Some dendrites have
voltage gated channels that can help amplify
signals along dendrites.
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Inhibition
IPSP are generated when ion channels are opened
causing hyperpolarization of the membrane. Ie.
GABA or glycine opens Cl- channels Shunting
Inhibition inward movement of Cl- anions will
negate the flow of positive ions.
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