LONGTERM POTENTIATION LTP

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LONG-TERM POTENTIATION (LTP) Introduction LTP as
a candidate mechanism for the activity-dependent
change in the strength of synaptic connections
LTP is a persistent increase in synaptic
strength (as measured by the amplitude of the
EPSP) that can be rapidly induced by brief neural
activity.
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• Anatomical background for Hippocampus
• two interlocking C-shaped regions (the
  hippocampus and the dentate gurus),
• main inputs entorhinal cortex
• three major afferent pathways (subiculum -gt CA1)
• Perforant pathway (subiculum -gt granule cells
  in dentate gyrus)
• Mossy fiber pathway (axons of the granule
  cells -gt pyramidal cells in the CA3)
• Schaffer collaterals (pyramidal cells in the
  CA3 -gt pyramidal cells in the CA1)

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• Perforant pathway (subiculum -gt granule
  cells in dentate gyrus)
• Mossy fiber pathway
• (axons of the granule cells -gt pyramidal
  cells in the CA3)
• Schaffer collaterals
• (pyramidal cells in the CA3 -gt pyramidal
  cells in the CA1)

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• The initial finding by Timothy Bliss and Terje
  Lomo (1973)
• Anaesthetized rabbit
• Brief, high-frequency stimulation of the
  perforant pathway input to the dentate gyrus
  produced a long lasting enhancement of the
  extracellular recorded field potential.

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Recording techniques In vivo (in awake and
freely moving animals, or in anesthetized
animals) in vitro (slice preparations)
Extracellar recordings intracellular recordings
Experimental design Stimulation of a bundle of
presynaptic axons recording of monosynaptic EPSP
Typical results for induction of LTP
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• The "classical properties" of LTP
• Cooperativity
• The probability of inducing LTP, or the magnitude
  of the resulting change, increases with the
  number of stimulated afferents.
• Associativity
• associativity was shown in preparations in
  which two distinct axonal inputs converged onto
  the same postsynaptic target
• Concurrent stimulation of weak and strong
  synapses to a given neuron strengthens the weak
  ones.
• Input specificity
• LTP is restricted to only the inputs that
  received the tenanic (high-frequency) stimulation
  

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• Underlying molecular mechanisms
• Introduction
• LTP requires some sort of additive effect
• High-frequency stimulation
• Activation of synapses and depolarization of the
  postsynaptic neuron must occur at the same time
• LTP (in area CA1) depends on certain changes at
  glutamate synapses,
• Types of glutamate receptors
• NMDA receptors
• Non-NMDA receptors
• At non-NMDA receptors,
• glutamate is excitatory
• Open channels for sodium ions

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• At NMDA receptors,
• Controls a calcium ion channel
• glutamate is neither excitatory nor inhibitory
• Ion channel is blocked by magnesium ions
• Activation of NMDA receptors requires both
  glutamate and depolarization, which lead to the
  removal of magnesium ions
• The NMDA receptors now respond actively to
  glutamate and admit large amount of Ca2 through
  their channels
• After induction of LTP, transmission at non-NMDA
  receptors is facilitated

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• LTP is induced via a cascade of neurochemical
  steps
• The entry of Ca2 ions into neurons activates
  some protein kinases (which are enzymes that
  catalyze phosphorylation, the addition of
  phosphate groups to protein molecules).
• One of the kinase, Calcium-calmodulin kinase (CaM
  kinase) remains activated once it is put into
  that state by Ca2, even if the level of Ca2
  subsequently falls
• The activated protein kinases also trigger the
  synthesis of proteins
• activate cAMP responsive element-binding protein
  (CREB)
• CREB -gt production of the transcription (mRNA) of
  immediate early genes (IEGs) -gt regulate the
  expression of particular late effector genes
  (LEGs) -gt synthesis of proteins
• Induction of LTP requires a retrograde signal,
  from the postsynaptic neuron to the presynaptic
  neuron

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