Download - Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt
![Page 1: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/1.jpg)
Functional dissection of the CA3-CA1 learning ruleFunctional dissection of the CA3-CA1 learning rule
Sam WangPrinceton University
http://synapse.princeton.edu/~sam/Wang-STDP.ppt
![Page 2: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/2.jpg)
Optical physiology andOptical physiology and synaptic plasticity:synaptic plasticity:
Shari GelberShari GelberDaniel O’ConnorDaniel O’ConnorDmitry SarkisovDmitry SarkisovShy ShohamShy ShohamMegan SullivanMegan SullivanGayle WittenbergGayle Wittenberg
Brain scaling andBrain scaling and evolution:evolution:
Mark BurishMark BurishDamon ClarkDamon ClarkKim Hatch HarrisonKim Hatch HarrisonHao Yuan KuehHao Yuan KuehJennifer ShultzJennifer ShultzMatt WagersMatt WagersKrysta WyattKrysta Wyatt
Laboratory of Sam WangLaboratory of Sam Wang
![Page 3: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/3.jpg)
Too many learning rules!
Abbott and Nelson,Nat. Neurosci.
![Page 4: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/4.jpg)
![Page 5: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/5.jpg)
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,…
![Page 6: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/6.jpg)
Plasticity at CA3-CA1: a separable process?
![Page 7: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/7.jpg)
• 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?
Questions at the CA3-CA1 synapse
![Page 8: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/8.jpg)
Nishiyama et al. 2000 Nature 408:58480 pairings at 5 Hz Cesium pipet solution
Pike et al. 1999Journal of Physiology 518:57140 pairings at 5 Hz Four epochs (10 pairings each) at 10-s intervals
Christie et al. 1996Learning and Memory 3:160900 pairings at 3 HzEpochs (30-60 pairings each) at 5-s intervals
At the CA3-CA1 synapse, pairing single APs gives…
…LTP.
…no change.
…LTD.
![Page 9: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/9.jpg)
At CA3-CA1 synapses, pairing of single spikes fails to induce potentiation
Single pre+post APs
100 pairings with t=0-7 ms (pre before post)
Pairing frequency 0.1-5 Hz
![Page 10: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/10.jpg)
However…
In Nishiyama et al. Cesium replaced Potassiumin the intracellular pipette solution
This will…-depolarize neuron -block A-type K channels in dendrite-broaden action potentials
![Page 11: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/11.jpg)
Potassium Cesium
Cs+
K+
pairings given at 5 Hz
![Page 12: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/12.jpg)
Cs+
K+
…can bursts of APs emulate Cs+?
![Page 13: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/13.jpg)
LTP induction requires postsynaptic bursting
![Page 14: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/14.jpg)
CA1 neurons fire bursts during theta oscillation
![Page 15: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/15.jpg)
Pairings must be given at high frequency
t
![Page 16: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/16.jpg)
Observations on the LTP learning rule
• Potentiation requires postsynaptic bursts
• Pairings are effective at 5 Hz (near theta)
…does depression have these requirements?
![Page 17: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/17.jpg)
LTD occurs under many timing conditions
All pairings given at 5 Hz
![Page 18: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/18.jpg)
Requirement Theta Bursting
LTP yes yes
LTD no no
![Page 19: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/19.jpg)
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.
![Page 20: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/20.jpg)
Why not explore parameter space exhaustively?
…because it’s exhausting!
![Page 21: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/21.jpg)
Shy Shoham
Uncaging in spatial patterns: High-throughput screening of neural responses
Resolution: <1 micron30,000 locations per second
![Page 22: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/22.jpg)
Subthreshold and spiking behavior for “natural” stimulation ensembles
0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000-100
-50
0
50
0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000-100
-50
0
50
0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000-100
-50
0
50
![Page 23: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/23.jpg)
Now play movie athttp://synapse.princeton.edu/~sam/shoham-oconnor-movie.avi
![Page 24: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/24.jpg)
Local amplification in dendritic branches
![Page 25: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/25.jpg)
![Page 26: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/26.jpg)
![Page 27: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/27.jpg)
![Page 28: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/28.jpg)
Strategies for separating LTD and LTP
![Page 29: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/29.jpg)
![Page 30: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/30.jpg)
LTD and LTP are separable
![Page 31: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/31.jpg)
![Page 32: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/32.jpg)
![Page 33: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/33.jpg)
![Page 34: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/34.jpg)
LTD is fully reversible
![Page 35: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/35.jpg)
LTP is not fully reversible!
![Page 36: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/36.jpg)
After being induced, LTP becomes locked in
![Page 37: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/37.jpg)
The starting distribution of CA3-CA1 synapses
>1 Hz
>10 Hz >10 Hz
![Page 38: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/38.jpg)
The CA3-CA1 learning rule
…butdissectable?
Complex…
![Page 39: Functional dissection of the CA3-CA1 learning rule Sam Wang Princeton University sam/Wang-STDP.ppt](https://reader036.vdocuments.site/reader036/viewer/2022062516/56649d605503460f94a41d09/html5/thumbnails/39.jpg)