Chapter Thirteen The Biology of Learning and Memory

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Chapter ThirteenThe Biology of Learning and
Memory
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Stress and Memory CNN Today
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Predicting Alzheimers Disease CNN Today
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Alzheimers Disease and the Brain CNN Today
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Aplysia and the Study of Learning

• D.O. Hebb proposed that when an axon successfully
  stimulates a cell it will be even more successful
  in the future
• Aplysia, a marine invertebrate, is a popular
  experimental animal
• has few neurons and it is easy to study behavior
  change as a result of neuronal activity
• touch results in the withdrawal of the siphon,
  mantle or gill
• often study the withdrawal response and learning

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Aplysia and the Study of Learning cont

• Habituation
• after repeated stimulation of gills the sensory
  neuron no longer increases action potentials to
  stimulate motor neuron
• Sensitization
• intense stimulus anywhere on skin excites
  facilitating neuron to release serotonin onto
  presynaptic terminals of sensory and excitatory
  neurons, prolonging neurotransmitter release
• Thus, changes in synaptic activity produces
  behavioral plasticity, i.e., change due to
  learning

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• Figure 13.19 Sensitization of the withdrawal
  response in Aplysia. Stimulation of the sensory
  neuron ordinarily excites the motor neuron,
  partly by a direct path and partly by stimulation
  of an excitatory interneuron. Stimulation of a
  facilitating interneuron releases serotonin to
  the presynaptic receptors on the sensory neuron,
  blocking potassium channels and thereby
  prolonging the release of neurotransmitter. This
  effect can be long-lasting. (Source After Kandel
  Schwartz, 1982.)

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Long-term Potentiation (LTP) and Depression (LTD)

• LTP a burst of stimulation from axons, e.g., 100
  excitations per second for 1-4 seconds onto
  dendrites results in potentiated synapses for
  minutes, days or weeks
• specificity only active synapses become
  strengthened
• cooperativity nearly simultaneous stimulation by
  two or more axons results in LTP
• associativity pairing a weak input with a strong
  input enhances later response to the weak input
• LTD prolonged decrease in response to a synaptic
  input where two or more axons have been active
  together at 1-4 times per second

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Biochemical Mechanisms of LTP in Hippocampus

• AMPA and NMDA receptors are involved in LTP
• glutamate receptors that open channels in
  postsynaptic neurons to let in one or more kinds
  of ions (ionotropic)
• AMPA receptors glutamate opens sodium channels
• similar to what we have studied

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Biochemical Mechanisms of LTP in Hippocampus cont.

• NMDA receptors normally blocked by magnesium but
  responds to glutamate when depolarized by AMPA
  receptors
• calcium enters and activates protein CaMKII,
  which is necessary for LTP, and sets several
  processes in motion
• structure of AMPA receptors change, becoming more
  responsive to glutamate
• some NMDA receptors change to AMPA receptors and
  increase their responsiveness to glutamate
• dendrites may build more AMPA receptors and make
  more branches
• Once established, LTP no longer depends on NMDA
  synapses

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• Figure 13.21 The AMPA and NMDA receptors during
  LTP. If one or (better) more AMPA receptors have
  been repeatedly stimulated, enough sodium enters
  to largely depolarize the dendrites membrane.
  Doing so displaces the magnesium ions and
  therefore enables glutamate to stimulate the NMDA
  receptor. Both sodium and calcium enter through
  the NMDA receptors channel.

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Biochemical Mechanisms of LTP in Hippocampus cont.

• Presynaptic changes
• stimulation of the postsynaptic cell releases a
  retrograde transmitter that feeds back to
  presynaptic cell
• increases presynaptic release of neurotransmitter
  and production of GAP-43, facilitating growth of
  axons
• Consolidation of LTP
• following training, LTP seen in hippocampus
  quickly and in cerebral cortex 90-180 minutes
  later
• drugs that block NMDA receptors within 2 weeks of
  training also block consolidation of long-term
  memory
• but, other studies found blocking NMDA for first
  week prolonged LTP and increased dendritic
  branching

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LTP and Behavior

• Neurons change early in training, a preliminary
  step before behavioral change
• Research with mice
• abnormal NMDA receptors impair learning
• more than normal NMDA receptors enhances learning
• drugs that block LTP block learning while drugs
  that facilitate LTP facilitate learning
• a lack of AMPA receptors creates deficits in LTP
  and memory
• over production of GAP-43 enhances learning and
  problem solving

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LTP and Behavior cont.

• Can drugs improve your memory?
• gingko biloba sometimes produces small benefits
  in Alzheimers patients or others with
  circulatory problems
• no research on combination of memory-boosting
  supplements