3.4

• Nerve-to-nerve transmission


  Very sophisticated
• Nerve-to-nerve transmission can be much more sophisticated than the simple input-output relationship that occurs at the skeletal muscle Neuro-Muscular Junction

  
• Transmitter-gated ion channels


  Post-synaptic response to the transmitter is very rapid because the transmitter directly influences the post-synaptic ion channels

  
• 1. protein coupled receptors


  Post-synaptic response to the transmitter is slower because of the intervening step of having to activate the G protein that then has to influence the post-synaptic ion channels
• 2nd messenger-gated channels


  Post-synaptic response to transmitter is slower still because of intervening steps of activating the G protein which then has to activate enzymes to produce 2nd messengers that then influence the post-synaptic ion channels

  
• Transmitter-gated and voltage-gated channels often have similar structures
• Transmitter-gated ion channels


  Selective only for the type of charge (e.g, Na+ & K+ can generally both go through the same AcetylCholine transmitter-gated channel)
• Excitatory transmitter-gated ion channels

  Net post-synaptic depolarization depends on the amount of Na+ entering the cell versus the amount of K+ leaving

  
• Inhibitory transmitter-gated ion channels

  Net post-synaptic hyperpolarization depends on the net amount of Cl- entering the cell or K+ leaving through their respective transmitter-gated channels

  
• Transmitter-gated ion channels


  Produce fast, brief post-synaptic voltage responses

  
• Mechanisms involving 2nd messengers

  Produce slower, longer-lasting responses that, in addition to voltage changes, can also involve other changes in the cell through effects at the nucleus
• An individual neuron can get both fast and slow synaptic inputs
• The same transmitter can produce both fast and slow effects, depending on the type of post-synaptic receptor to which it binds

  
• Post-synaptic receptors


  Always membrane-bound

  
• Receptors for transmitter


  May form ion channels or be coupled to G proteins (GPCRs)
• Receptors that form ion channels

  Always made up of 5 protein sub-units
• Receptors coupled to G proteins


  Always made up of a single polypeptide with 7 transmembrane segments
• Excitatory synapses


  Produce a depolarisation of the membrane potential of the post-synaptic cell

  
• Inhibitory synapses


  Produce a hyperpolarization of the membrane potential of the post-synaptic cell

  
• A pre-synaptic AP will result in the fusion of many vesicles of transmitter with the pre-synaptic membrane, resulting in the release of large numbers of transmitter

  
• Acetyl Choline (ACh) is the non-peptide neurotransmitter used to signal the information from the motor neuron to the muscle fibre at the end plate

  
• The figure above shows the change produced in the limiting case by a single vesicle of transmitter. In fact, a pre-synaptic AP will result in the fusion of many vesicles of transmitter with the pre-synaptic membrane, resulting in the release of large numbers of transmitter.

  
• The post-synaptic effects will simply be scaled for size, in proportion to the amount of transmitter released, since more transmitter means binding to more receptors to produce a larger post-synaptic response.

  
• AcetylCholine is the transmitter at the NeuroMuscular Junction

  
• Life cycle of AcetylCholine


  1. Precursor Acetyl-CoenzymeA (AcCoA) produced in mitochondria & released into cytoplasm

  2. Combines with Choline to produce Acetyl Choline

  3. Acetyl Choline stored in vesicles

  4. Fusion of vesicles with terminal membrane releases ACh into synaptic cleft

  5. ACh broken down to release Acetate and Choline

  6. Choline re-absorbed by pre-synaptic terminal

  
• Packaging of ACh into vesicles

  • Involves an antiport ion pump which exchanges H+ from within the vesicle for ACh molecules in the cytoplasm
  • Each vesicle contains about 6,000-10,000 molecules of ACh

  
• Information flow between neurons is not as "efficient" as between neurons and skeletal muscle
• A single AP in a motor neuron results in a large change in the skeletal muscle fibre's resting membrane potential, called the end plate potential

  
• One AP in a neuron produces a much smaller change in post-synaptic resting membrane potential produced when the post-synaptic target is another neuron

  
• Divergence


  Branching of one neuron so as to innervate others
• Convergence


  Innervation by many cells of a single cell
• Most neurons get many hundreds to thousands of synaptic inputs that have to be integrated

  
• Convergence and divergence of information flow in the nervous system

  • Allows each neuron to receive multiple inputs, some excitatory and others inhibitory
  • Neurons have to sum their many excitatory and inhibitory inputs before "deciding" to respond with an Action Potential
  • Inputs can produce rapid or slow responses in the post-synaptic neuron
  • Synapses on different parts of the neuron vary in their effectiveness

  
• Excitatory Post-Synaptic Potential (EPSP)

  Larger depolarisation of the resting membrane potential of the post-synaptic cell produced by a pre-synaptic neuron releasing more transmitter

  
• Inhibitory Post-Synaptic Potential (IPSP)


  Larger hyperpolarization of the resting membrane potential of the post-synaptic cell produced by a pre-synaptic neuron releasing more transmitter

  
• EPSPs bring the membrane potential closer to the threshold for an Action Potential, increasing the likelihood of the post-synaptic cell producing an Action Potential

  
• IPSPs take the membrane potential further from the threshold for an Action Potential, decreasing the likelihood of the post-synaptic cell producing an Action Potential

  
• Properties of PSPs that differ from APs

  • Vary in amplitude
  • Vary in duration
  • Spread passively (electronically)
  • Decay with distance
• EPSPs and IPSPs spread passively (electronically), and decay with distance
• The threshold to produce an AP varies across the neuron, with the axon hillock generally having the greatest density of voltage-gated Na+ channels