synaptic plasticity DENT/OBHS 131 Neuroscience 2009

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

learning & memory in taxi drivers PET study during recall of London route (Maguire et al, 1997)

Papez circuit / loop

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)

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 ”

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

Can synaptic plasticity explain learning? CS (neutral) - no response US - UR After pairing: CS - CR

Learning Objective #1 Understand the properties of long-term potentiation (LTP) that define it as a model of experience-dependent synaptic plasticity

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)

properties of LTP

Learning Objective #2 Discuss the characteristics that make NMDA receptors coincident detectors cable of initiating associative information storage (Pavlov’s dog)

cellular mechanisms underlying LTP induction maintenance

AP5 control excitatory synaptic transmission NMDA vs non-NMDA synaptic transmission

LTP depends specifically on NMDA receptor activation  AP5 prevents high frequency-induced LTP (Collingridge et al, 1983)

what is special about NMDA receptors? voltage-gated channels: voltage ligand-gated channels: transmitter NMDA receptors: both out in Mg+

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:

how does the NMDA receptor cause a change in synaptic strength?

synaptic transmission is unreliable increased transmitter release altered or new receptors new synapses

Johnson & Wu (1995) hippocampal “integrated circuit”

associative pattern storage from McNaughton & Morris (1987)

Learning Objective #3 Describe the relationship between NMDA receptors, LTP and behavioral memory

spatial memory taskvisual task “Morris” water maze Morris et al (1990) NMDA receptor-dependent learning

LTPdecay Castro et al (1989) LTP and learning saturation of LTP prevents learning a new spatial task new learning can occur after LTP decay

diffuse storage in cortex? computational theories  e.g., Marr (1970’s) sensory input to neocortex  stored by association  repetition - association  partial pattern recall