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Functional dissection of the CA3-CA1 learning rule. Sam Wang Princeton University http://synapse.princeton.edu/~sam/Wang-STDP.ppt. Laboratory of Sam Wang. Brain scaling and evolution: Mark Burish Damon Clark Kim Hatch Harrison Hao Yuan Kueh Jennifer Shultz Matt Wagers Krysta Wyatt.
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Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University http://synapse.princeton.edu/~sam/Wang-STDP.ppt
Laboratory of Sam Wang Brain scaling and evolution: Mark Burish Damon Clark Kim Hatch Harrison Hao Yuan Kueh Jennifer Shultz Matt Wagers Krysta Wyatt Optical physiology and synaptic plasticity: Shari Gelber Daniel O’Connor Dmitry Sarkisov Shy Shoham Megan Sullivan Gayle Wittenberg
Too many learning rules! Abbott and Nelson, Nat. Neurosci.
CA3-CA1 synapse of hippocampus Rich history of extracellular and single-cell recording The cell biology and plasticity literature is vast One synapse per connection Has AMPA, NMDA, mGluR,…
Questions at the CA3-CA1 synapse • Is timing between single spikes sufficient to describe the actual learning rule? • How different are the requirements for potentiation and depression? Are these full inverses of each other? • How might the learning rule map to behavior? • Can cell biology help clarify these issues conceptually?
At the CA3-CA1 synapse, pairing single APs gives… Nishiyama et al. 2000 Nature 408:584 80 pairings at 5 Hz Cesium pipet solution …LTP. Pike et al. 1999 Journal of Physiology 518:571 40 pairings at 5 Hz Four epochs (10 pairings each) at 10-s intervals …no change. Christie et al. 1996 Learning and Memory 3:160 900 pairings at 3 Hz Epochs (30-60 pairings each) at 5-s intervals …LTD.
At CA3-CA1 synapses, pairing of single spikes fails to induce potentiation Single pre+post APs 100 pairings with Dt=0-7 ms (pre before post) Pairing frequency 0.1-5 Hz
However… In Nishiyama et al. Cesium replaced Potassium in the intracellular pipette solution This will… -depolarize neuron -block A-type K channels in dendrite -broaden action potentials
Potassium Cesium Cs+ K+ pairings given at 5 Hz
Cs+ K+ …can bursts of APs emulate Cs+?
Dt Pairings must be given at high frequency
Observations on the LTP learning rule • Potentiation requires postsynaptic bursts • Pairings are effective at 5 Hz (near theta) …does depression have these requirements?
LTD occurs under many timing conditions All pairings given at 5 Hz
Requirement Theta Bursting LTP yes yes LTD no no
Conclusions so far • Potentiation and depression have different general induction requirements. • Potentiation: active exploration (causal, bursts, 5 Hz) • Depression: many conditions • During theta, the rule acts like a phase detector. • At other times, the rule is depression-only.
Why not explore parameter space exhaustively? …because it’s exhausting!
Uncaging in spatial patterns: High-throughput screening of neural responses Resolution: <1 micron 30,000 locations per second Shy Shoham
Subthreshold and spiking behavior for “natural” stimulation ensembles
Now play movie at http://synapse.princeton.edu/~sam/shoham-oconnor-movie.avi
The starting distribution of CA3-CA1 synapses >1 Hz >10 Hz >10 Hz
The CA3-CA1 learning rule Complex… …but dissectable?