memory - Drugs & addiction

• Memory in brain

  • 1900 - Cajal proposed synaptic connections between neurons mediating behaviour
  • = not static but become modified by learning
  • modifications can persist & serve as memory
• Memory in brain - strength changes:

  • strength of synaptic connections can be increased by sensitization (following prolonged stimulation) & CC, & reduced by habituation
  • = storage of non-declarative memory embedded in neural circuit that produces behaviour
• Hippocampus & memory consolidation

  • amnesia - deficity in memory - result of brain damage
  • anterograde - inability to form new LTM following insult/ injury
  • retrograde - inability to recall memories preceeding insult
• H.M.

  • Surgery for epilepsy - Removal of both sides of inner part of temporal lobe, including hippocampus
  • Normal working memory (digit span), perceptual learning, instrumental & classical conditioning
  • Disrupted transfer from ST to LT memory → dense anterograde amnesia
• H.M. implications

  • Hippocampus not necessary for STM
  • Previous declarative memory Intact = hippocampus not repository of LTM
  • Hippocampus critical for consolidation of new memories
• Cellular basis of all long term learning - Long term potentiation

  • If a weak & strong input act on a neuron at the same time, the weak synapse becomes stronger (Hebbian learning)
  • = when same weak input given again response of target cell increases (LTP=memory)
• For LTP to be induced, 2 things must be in place:


  • postsynaptic cell must be depolarized (by strong input)
  • postsynaptic cell must receive additional input (weak input)
• Long-Term Potentiation (LTP): synaptic mechanisms

  • Excitatory neurotransmitter - Glutamate
  • NMDA receptors

        Contain transmembrane channel for Ca2+

        Double gated – transmitter & voltage

  • Glutamate binds to NMDA
  • Other receptors depolarize cell, removing Mg+ block

  → Need presynaptic + postsynaptic activity
• Long-Term Potentiation : synaptic mechanism 2

  • Ca2+ channel opens, Ca2+ activates enzyme

  Triggers

  • insertion of more AMPA receptors into membrane
  • retrograde messenger (NO) leads to increased presynaptic glutamate release

  → Stronger synaptic response, bigger EPSPs
• Long term depression

  • Low-frequency stimulation of synapse, or firing of 2 inputs out of phase = weakening
  • Inputs not contributing to postsynaptic firing = weakened

  = learning instantiated in brain - as memory