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Learning rules in the hippocampus and cerebellum
Sam Wang
Princeton University
synapse.princeton.edu
Sam Wang’s laboratory and collaborators
Optical physiology and synaptic plasticity
Eugene Civillico, Tycho Hoogland, Bernd Kuhn, Megan
Lee, Daniel O’Connor, Dmitry Sarkisov, Shy Shoham,
Megan Sullivan, Gayle Wittenberg
Lausanne: Fritjof Helmchen, Werner Goebel, Axel
Nimmerjahn
Princeton: S. Jane Flint, Lynn Enquist, David Tank,
Dan Dombeck
RIKEN: Junichi Nakai
Brain scaling and evolution
Mark Burish, Damon Clark, Kim Harrison, Aline
Johnson, Jennifer Shultz, Matt Wagers, Krysta Wyatt
NYU: Patrick Hof
Kirksville College of Osteopathic Medicine: Lex Towns
http://synapse.princeton.edu
Memento (2001)
Donald Hebb: The Cell-Assembly (1949)
“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)
“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.”
B
A
D
E
C
Memory is proposed to
be mediated by replayed
sequences of activity
Synaptic 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
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)
Brain architecture
Brain
~1011 neurons
Cortical column
~105 neurons
Neuron
~104 synapses
10cm
1mm
1mm
Plasticity is usually measured across many synapses…
30,000
synapses
…what are its properties at
single synapses?
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,…
Plasticity at CA3-CA1: a separable
process?
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?
• How might the learning rule map to behavior?
• What unitary events underlie plasticity in the
synaptic ensemble?
Calmodulin-dependent protein kinase II: a molecular switch
J. Lisman, H. Schulman, and H. Cline (2002)
Nature Rev. Neurosci. 3:175
Delivery of
glutamate receptors
Plasticity occurs in sudden steps
10 pA
5 ms
O’Connor, Wittenberg and Wang (2005) PNAS 102:9679
Potentiation and depression events are symmetrically sized
Unitary properties of plasticity at CA3-CA1 synapses
All-or-none
Single steps up and down
Steps are of similar size
Unitary events can account for the time course of
plasticity
Binary transitions
in single synapses
LTD is fully reversible
LTP is not fully reversible!
After being induced, LTP becomes locked in
The starting distribution of CA3-CA1 synapses
>1 Hz
>10 Hz
>10 Hz
Ensemble learning rules
Gayle Wittenberg
L.F. Abbott and S.B. Nelson (2000)
Nat. Neurosci.
The CA3-CA1 synapse of hippocampus
Sorra and Harris (1993)
Rich history of extracellular and single-cell recording
The cell biology and plasticity literature is vast
Has AMPA, NMDA receptors, kinases, phosphatases…
One synapse per connection
Spike timing-dependent plasticity at CA3-CA1 synapses
Daniel O’Connor & Gayle Wittenberg
J. Neurophysiol. 2005 94:1565
PNAS 2005 102:9679
J. Neurosci. 2006 26:6610
During active exploration, CA1 neurons fire repeated bursts
Huxter et al. (2003) Nature 425:828
Wittenberg & Wang 2006
Components of bidirectional plasticity
The potentiation rule
Requires postsynaptic bursts
Requires high frequency pairings
The depression rule
Broad timing-dependence
Requires prolonged pairing
Complications
•
•
•
•
Spreading plasticity
Priming
Homeostatic plasticity
Subcellular instruction
A simple passive dendritic arbor?
http://www.wam-bamm.org/WB05/Tutorials/genesis-intro/genesis-intro.html
No!
Backpropagation of
somatic sodium spike
Forward propagation of
dendritic calcium spike
Häusser, Spruston,
Stuart
Science 2000
(from Vetter, Roth,
Hausser
J Neurophysiol 2001)
20,000 locations
per second
Imaging neural activity in the intact cerebellum
Sullivan, Nimmerjahn, Sarkisov, Helmchen and Wang (2005) J. Neurophysiol.
Calcium responses in Purkinje cell dendrites
Evidence for regional calcium events in
vivo
Megan Sullivan
The end