Molecular mechanisms

• Plasticity


  Refers to changes in synaptic strength
• Prolonged increase of synaptic strength = long-term potentiation (LTP)

  Prolonged weakness = long-term depression (LTD). Both excitatory and inhibitory synapses can be subject to either of these, and we need a balance to keep a healthy brain (neither one is all good or all bad)
• Bliss and Lomo put electrodes along the perforant pathway and the dentate gyrus, simulating the pathway and gave 100 Hz shocks for 3 seconds, which made the axons fore 300 times total. This made the fEPSP go crazy, and the long-term potentiation lasted over a year
• Field excitatory post-synaptic potential (fEPSP)


  Extracellular way of measuring the force of neurons firing. The more that depolarize, the higher it is
• AMPA 


  Glutamate receptors that have ligand-gated ion channels that allow cations, mostly Na+ , to enter, causing depolarization
• NMDA


  Ionotropic glutamate receptors that have an Mg2+ ion in the middle that is attracted in but too big to enter so it seals the protein. When it activates the Mg2+ ion leaves and lets Ca2+ enterand activate the enzyme CaMKII
• CaMKII


  Calcium-calmodulin dependant protein kinase II
• CaMKII does 3 things to promote LTP:

  • Phosphorylates amino acid residue onto AMPA which makes them bring in more ions
  • Contributes to bringing more AMPA receptors to the surface
  • Interacts with transcription factor CREB which leads to more mRNA coding for more AMPA receptors
• Long-term potentiation (LTP)


  An enhancement of a signal that persists over the course of hours because of heightened synaptic activity
• 2 conditions must be met before NMDA receptors can activate:

  • Postsyaptic cell has to be depolarized so the Mg2+ gets unstuck
  • Glutamate must activate it
• Coincidence detector


  When two separate criteria have to be met in order to activate a receptor (like NMDA)
• Silent synapse


  A synapse with NDMA but no AMPAs so they can't fire even if there's glutamate present. These get fewer and fewer as we age, because we get more synapses
• Long-term depression


  When a circuit of neurons becomes less effective for prolonged periods of time (like in sensitization)
• Aplysia californica


  Marine mollusk where LTD was first practiced on my brushing its gills over and over until they got sensitized and the retracting reflex got dampened
• Endocannabinoid mediated LTD


  When neurons are have their release proablilities released by EcBs
• Nitric oxide can diffuse through cells and activate the intracellular receptor soluble guanylate cyclase (sGC) which changes the signalling molecule cGMP which can lead to LTD or LTP
• Paired pulse facilitation and paired pulse depression pair together to form two pulses (necessary for it to be considered plasticity). One might be bigger than the other because of the time difference, and that ratio is called the paired pulse ratio