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LTP
Long Term Potentiation
Long Term Potentiation:
• Potentiation: enhancement of one agent by another so
that the combined effect is greater than the sum of the effects
of each one alone.
• In neuroscience, potentiation refers to the
persistent strengthening of synapses based on
recent patterns of activity.
Graph illustrates LTP. Notice the strength of EPSP after
potentiation has occurred.
Synaptic Plasticity:
• Ability of synapses to strengthen or weaken
over time, in response to increases or
decreases in their activity.
• Plasticity results from the alteration of the
number of neurotransmitter receptors located
on a synapse and neurotransmitter
production.
Synaptic Plasticity:
Neurotransmitters:
• Endogenous chemicals responsible for
synaptic transmission.
• Glutamate- (excitatory) plays a key role in LTP,
memory, and learning.
Receptors:
• AMPA (α-amino-3-hydroxy-5-methylisoxazole-4- propionic acid)
– Receptor for glutamate
– Allows influx of Na+ ions
– Produces EPSP
• NMDA (N-methyl d-aspartate)
– Unblocked (opens) when neuron depolarizes
– Allows rapid influx of Ca2+ ions
Ca2+ influence on LTP:
• Rapid influx of Ca2+ into the postsynaptic
neuron triggers the production of several
protein kinases including CaMKII, PKC, PKA,
and MAPK.
• Protein kinases regulate cellular pathways;
most importantly signal transduction.
CaMKII
Protein Kinase Influence on LTP:
• Early LTP:
– Increase activity of existing AMPA receptors
– Insertion of additional AMPA receptors on
postsynaptic membrane
• Late LTP:
– Initiates protein synthesis and gene expression
– Increase dendritic spine number, surface area, and
synthesis of AMPA receptors.
Retrograde Signaling:
• Increases release of neurotransmitters by
presynaptic neuron.
• Requires message from postsynaptic neuron
to presynaptic neuron (retrograde)
• Messenger: nitric oxide
Hippocampus:
• Studies of LTP have
involved the
hippocampus.
• Important structure of
the brain involved in
memory and learning.
• Located along the
medial surface of the
brain.
Morris Water Maze:
• 1986 Richard Morris tested spatial memory of
rats by pharmacologically modifying their
hippocampus.
• Rats with NMDA receptors blocked were
significantly impaired.