The Doogie mouse

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The Doogie mouse
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Synaptic plasticity

• Both electrical and chemical synapses can change
  temporally and spatially.
• Changes in synaptic efficacy is synaptic
  plasticity.
• Chemical synapses undergo metabolic regulation to
  maintain homeostasis (Ex ACh).
• Changes in synaptic efficacy (change in amplitude
  of response) should last.

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Synaptic efficacy

• Synaptic facilitation (posttetanic potentiation)
  follows tetanic stimulation of presynaptic
  neuron.
• Synaptic depression (or antifacilitation)
• Both affect the amount of NTs released.
• Habituation is a decrease in the sensitivity of a
  synapse.
• Sensitization is prolonged enhancement of a
  synapse to stimulation.

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Figure 12.22 Synaptic facilitation and
antifacilitation
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Figure 12.23 Habituation and sensitization in
Aplysia gill withdrawal (Part 1)
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Figure 12.23 Habituation and sensitization in
Aplysia gill withdrawal (Part 2)
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Behavioral sensitization

• Changes in EPSP are correlated with changes in
  the quanta of NT released.
• Habituation is a progressive long-lasting
  inactivation of Ca2 channels.
• Sensitization occurs at the sensory-to-motor
  synapse.
• Presynaptic facilitation underlies behavioral
  sensitization
• Presynaptic facilitation is caused by an influx
  of Ca2
• In Aplysia 5-HT increases the amount of cAMP in
  the sensory terminals which phosphorylates the K
  channels and leads to a decrease in the K
  current.

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Figure 12.24 A model of Aplysia sensitization
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Short term and long term effects

• Short term habituation lasts about an hour.
• Requires changes in synaptic mechanisms
• Long term habituation can persist for up to 3
  weeks.
• Requires protein synthesis
• High levels of cAMP activate cAMP-dependent
  protein kinase which activates gene transcription
  via cAMP response element-binding protein (CREB).
• Habituation and sensitization are nonassociate
  learning.

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Figure 12.25 Classical conditioning in Aplysia
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LTP in hippocampus

• Long term potentiation is a long lasting
  enhancement of synaptic transmission following
  intense stimulation.
• You need many presynaptic neurons to depolarize
  the postsynaptic CA1 cell.
• Any synapse that is active while the postsynaptic
  cell is strongly depolarized will be potentiated
  for hours (in slices), weeks (in vivo).

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Hebbian learning

• Learning depends on the pre and postsynaptic
  cells being depolarized at the same time.
• Neurons that fire together wire together.
• A synapse that undergoes a long term change in
  strength is called a Hebbian synapse

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Figure 12.26 Long-term potentiation in the
hippocampus (Part 1)
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Figure 12.26 Long-term potentiation in the
hippocampus (Part 2)
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Hippocampal LTP

• Depends on 2 glutamate receptors--N-methyl-D-aspar
  tate (NMDA) receptors and non-NMDA receptors.
• Non-NMDA receptors produce fast EPSPs.
• NMDA receptors only work when the cell is
  depolarized

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Figure 12.27 Induction and maintenance of LTP in
the hippocampus (Part 1)
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Figure 12.27 Induction and maintenance of LTP in
the hippocampus (Part 2)
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The Doogie Mice

• Joe Tsien and coworkers engineered a mouse that
  over expressed the juvenile subunit of NMDA
  receptors.
• Juvenile subunit remains open longer and allows
  more calcium to enter.
• Doogie mice remember novel stimuli longer and
  learn more easily