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synaptic plasticity DENT/OBHS 131 Neuroscience 2009
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Learning objectives 1.Understand the properties of long-term potentiation (LTP) that define it as a model of experience-dependent synaptic plasticity 2.Discuss the characteristics that make NMDA receptors coincident detectors cable of initiating associative information storage (Pavlov’s dog) 3.Describe the relationship between NMDA receptors, LTP and behavioral memory
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learning & memory in taxi drivers PET study during recall of London route (Maguire et al, 1997)
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Papez circuit / loop
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place cells / maps some pyramidal cells in the hippocampus (and other parts of Papez circuit) have preferred spatial orientations & place maps (O’Keefe & Dostrovsky, 1971)
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Hebbian learning….in theory longer term plasticity Hebbian learning Hebb (1949) hypothesized that “ if one neuron frequently takes part in exciting another, some growth process or metabolic change takes place in one or both cells and the strength of their connection increases ”
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muscle motor neuron pre post control muscle motor neuron nmj Synapses are plastic synapses “remember” previous activity short-term, e.g. post-tetanic potentiation at the nmj time
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Can synaptic plasticity explain learning? CS (neutral) - no response US - UR After pairing: CS - CR
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Learning Objective #1 Understand the properties of long-term potentiation (LTP) that define it as a model of experience-dependent synaptic plasticity
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Long-term potentiation (LTP) before after amplitude time (hrs) first demonstration of LTP high-frequency train rapid induction lasts weeks in vivo Bliss & Lomo (1973)
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properties of LTP
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Learning Objective #2 Discuss the characteristics that make NMDA receptors coincident detectors cable of initiating associative information storage (Pavlov’s dog)
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cellular mechanisms underlying LTP induction maintenance
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AP5 control excitatory synaptic transmission NMDA vs non-NMDA synaptic transmission
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LTP depends specifically on NMDA receptor activation AP5 prevents high frequency-induced LTP (Collingridge et al, 1983)
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what is special about NMDA receptors? voltage-gated channels: voltage ligand-gated channels: transmitter NMDA receptors: both + - + +++ - - - out in Mg+
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NMDA receptor: a molecular switch co-incidence detector requires both presynaptic activity (glutamate) and postsynaptic depolarization (relieve Mg block) satisfies Hebbian co-incidence rules explains LTP properties:
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how does the NMDA receptor cause a change in synaptic strength?
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synaptic transmission is unreliable increased transmitter release altered or new receptors new synapses
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Johnson & Wu (1995) hippocampal “integrated circuit”
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associative pattern storage from McNaughton & Morris (1987)
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Learning Objective #3 Describe the relationship between NMDA receptors, LTP and behavioral memory
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spatial memory taskvisual task “Morris” water maze Morris et al (1990) NMDA receptor-dependent learning
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LTPdecay Castro et al (1989) LTP and learning saturation of LTP prevents learning a new spatial task new learning can occur after LTP decay
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diffuse storage in cortex? computational theories e.g., Marr (1970’s) sensory input to neocortex stored by association repetition - association partial pattern recall
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