Exam 3

• Facilitation


  A rapid increase in synaptic strength that occurs when two or more action potentials invade the presynaptic terminal within a few milliseconds of each other
• Augmentation


  An activity-dependent form of short-term synaptic plasticity that enhances synaptic transmission over a time course of a few seconds
• Potentiation


  An activity-dependent form of short-term synaptic plasticity that enhances synaptic transmission over a time course of up to a few minutes
• Depression

  A short-term decrease in synaptic strength resulting from the depletion of synaptic vesicles at active synapses
• Steps of facilitation and augmentation

  1. 2 presynaptic action potentials elicit 2 EPSPs, the second one is larger
  2. Ca2+ removed slower than additional Ca2+ entering from the second action potential
  3. Increased neurotransmitter release
• Long-term potentiation

  Causes changes in the strength of synaptic connections, protein levels, and structural changes in the pre and post-synaptic processes
• Trisynaptic circuit of the hippocampus

  1. Entorhinal cortex gathers information
  2. Perforant pathway brings information into the Dentate Gyrus of hippocampus
  3. Granule cells to CA3 via mossy fibers
  4. CA3 projects to CA1 via the Schaffer Collateral pathway
• Electrical stimulation of Schaffer collaterals generate EPSPs in the postsynaptic CA1 pyramidal neurons
• Long-term depression is induced by low-frequency stimulation over a prolonged time
• Stimulating pre, then post-synaptic neurons causes...

  Long-term potentiation (EPSC up)
• Stimulating post, then pre-synaptic neurons causes...

  Long-term depression (EPSC down)
• Hebb's rule

  Cells that fire together wire together
• Long-term potentiation is dependent on...

  NMDA
• Addition of postsynaptic AMPA receptors during LTP

  LTP increases glutamate response of a dendritic spine due to an increase in the number of AMPA receptors on the spine. AMPA receptors move from the cytosol to the plasma membrane of the spine.
• Steps of AMPAR change in localization:

  1. Glutamate released from presynaptic neuron
  2. Activates AMPAR already at synaptic site
  3. NMDAR are activated if post-synaptic cell depolarized sufficiently
  4. Ca2+ activates CAMKII and PKC in dendrite
  5. CAMPKK and PKC phosphorylate downstream targets, including AMPAR
  6. Facilitates trafficking of AMPAR from recycling endosomes to the membrane
  7. Inserted at extrasynaptic regions
  8. DIffuse to synaptic regions
  9. Increase spine's sensitivity to glutamate
• Silent synapses

  Glutamatergic synapses that have NMDAR, but not AMPAR at the plasma membrane
• Protein synthesis in maintaining LTP

  Treatment with an inhibitor of protein synthesis causes LTP to decay within a few hours after the high-frequency stimulation
• Mechanisms responsible for long-term changes in synaptic transmission during LTP:

  1. NMDA activation via Ca2+
  2. Ca2+ Calmodulin
  3. Calmodulin regulates CaMKII and IV
  4. CAMK activates PKA
  5. PKA activates CREB
  6. CREB activates ubiquitin ligase, C/EBP, ERG1, c-fos, TFs, CPEB
• In LTD, low levels of Ca2+ decrease sensitivity to....

  Glutamate