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Learning rules in the hippocampus and cerebellumLearning rules in the hippocampus and cerebellum
Sam WangPrinceton University
synapse.princeton.edu
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Optical physiology and synaptic plasticityOptical physiology and synaptic plasticity
Eugene Civillico, Tycho Hoogland, Bernd Kuhn, Megan Eugene Civillico, Tycho Hoogland, Bernd Kuhn, Megan Lee, Daniel O’Connor, Dmitry Sarkisov, Shy Shoham, Lee, Daniel O’Connor, Dmitry Sarkisov, Shy Shoham, Megan Sullivan, Gayle WittenbergMegan Sullivan, Gayle Wittenberg
Lausanne: Fritjof Helmchen, Werner Goebel, Axel Lausanne: Fritjof Helmchen, Werner Goebel, Axel NimmerjahnNimmerjahn
Princeton: S. Jane Flint, Lynn Enquist, David Tank, Princeton: S. Jane Flint, Lynn Enquist, David Tank, Dan DombeckDan Dombeck
RIKEN: Junichi NakaiRIKEN: Junichi Nakai
Brain scaling and evolutionBrain scaling and evolution
Mark Burish, Damon Clark, Kim Harrison, Aline Mark Burish, Damon Clark, Kim Harrison, Aline Johnson, Jennifer Shultz, Matt Wagers, Krysta WyattJohnson, Jennifer Shultz, Matt Wagers, Krysta Wyatt
NYU: Patrick HofNYU: Patrick Hof
Kirksville College of Osteopathic Medicine: Lex TownsKirksville College of Osteopathic Medicine: Lex Towns
Sam Wang’s laboratory and collaboratorsSam Wang’s laboratory and collaborators
http://synapse.princeton.eduhttp://synapse.princeton.edu
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Memento (2001)
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“When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.”
Donald Hebb: The Cell-Assembly (1949)
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“When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.”
Donald Hebb: The Cell-Assembly (1949)
Memory is proposed tobe mediated by replayed
sequences of activity
A B
CD E
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Synaptic learning rulesSynaptic learning rules
• Learning rules: mapping activity to plasticity
• Hippocampal learning rules– Plasticity at the CA3-CA1 synapse– Saturation and all-or-none storage– Timing-dependent and higher-order learning rules
• Cerebellar learning rules– Plasticity at the parallel fiber-Purkinje cell synapse– A reverse timing rule– Coincidence detection at the IP3 receptor
• Beyond spike-based rules
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The human brain
• Size: 1.2 kg (total body weight 70 kg)
• Processing units:1011 neurons, 1015 synapses
• Power usage:12 W (total energy budget 70 W)
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Brain architecture
10cm
Brain ~1011 neurons
Cortical column ~105 neurons
1mm
m
Neuron ~104 synapses
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Plasticity is usually measured across many synapses…
30,000 synapses
…what are its properties at single synapses?
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CA3-CA1 synapse of hippocampus
Rich history of extracellular and single-cell recordingThe cell biology and plasticity literature is vastOne synapse per connectionHas AMPA, NMDA, mGluR,…
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Plasticity at CA3-CA1: a separable process?
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• Is timing between single spikes sufficient to describe the actual learning rule?
• How different are the requirements for potentiation and depression?
• How might the learning rule map to behavior?
• What unitary events underlie plasticity in the synaptic ensemble?
Questions at the CA3-CA1 synapse
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Calmodulin-dependent protein kinase II: a molecular switch
J. Lisman, H. Schulman, and H. Cline (2002)Nature Rev. Neurosci. 3:175
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Delivery of glutamate receptors
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10 pA
5 ms
Plasticity occurs in sudden steps
O’Connor, Wittenberg and Wang (2005) PNAS 102:9679
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Potentiation and depression events are symmetrically sized
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Unitary properties of plasticity at CA3-CA1 synapses
All-or-none
Single steps up and down
Steps are of similar size
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Unitary events can account for the time course of plasticity
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Binary transitionsin single synapses
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LTD is fully reversible
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LTP is not fully reversible!
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After being induced, LTP becomes locked in
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The starting distribution of CA3-CA1 synapses
>1 Hz
>10 Hz >10 Hz
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Ensemble learning rules
L.F. Abbott and S.B. Nelson (2000)Nat. Neurosci.
Gayle Wittenberg
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The CA3-CA1 synapse of hippocampus
Rich history of extracellular and single-cell recordingThe cell biology and plasticity literature is vastHas AMPA, NMDA receptors, kinases, phosphatases…One synapse per connection
Sorra and Harris (1993)
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Spike timing-dependent plasticity at CA3-CA1 synapses
Daniel O’Connor & Gayle WittenbergJ. Neurophysiol. 2005 94:1565
PNAS 2005 102:9679J. Neurosci. 2006 26:6610
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During active exploration, CA1 neurons fire repeated bursts
Huxter et al. (2003) Nature 425:828
Wittenberg & Wang 2006
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The potentiation rule
The depression rule
Requires postsynaptic burstsRequires high frequency pairings
Broad timing-dependenceRequires prolonged pairing
Components of bidirectional plasticity
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Complications
• Spreading plasticity• Priming• Homeostatic plasticity• Subcellular instruction
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Häusser, Spruston, StuartScience 2000(from Vetter, Roth, HausserJ Neurophysiol 2001)
Backpropagation of somatic sodium spike
Forward propagation of dendritic calcium spike
No!
A simple passive dendritic arbor?
http://www.wam-bamm.org/WB05/Tutorials/genesis-intro/genesis-intro.html
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20,000 locations per second
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Imaging neural activity in the intact cerebellum
Sullivan, Nimmerjahn, Sarkisov, Helmchen and Wang (2005) J. Neurophysiol.
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Calcium responses in Purkinje cell dendrites
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Evidence for regional calcium events in vivo
Megan Sullivan
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The end
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