Long-term synaptic plasticity. N500, 6 Sept., 2016

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Transcription:

Long-term synaptic plasticity N500, 6 Sept., 2016

We just finished describing short-term synaptic changes

What about long-term changes?

How does the brain store information?

Outline Origins of the synaptic hypothesis of memory The hippocampus and the tragic case of H.M. The discovery of Long term potentiation (LTP) Associative and Hebbian LTP Spike-timing dependent plasticity (STDP) Induction and expression Long-term depression (LTD) The BCM rule

Outline Origins of the synaptic hypothesis of memory The hippocampus and the tragic case of H.M. The discovery of Long term potentiation (LTP) Associative and Hebbian LTP Spike-timing dependent plasticity (STDP) Induction and expression Long-term depression (LTD) The BCM rule

S.Seung, MIT

S.Seung, MIT

S.Seung, MIT

Outline Origins of the synaptic hypothesis of memory The hippocampus and the tragic case of H.M. The discovery of Long term potentiation (LTP) Associative and Hebbian LTP Spike-timing dependent plasticity (STDP) Induction and expression Long-term depression (LTD) The BCM rule

The case of H.M. Surgery to prevent continued epileptic seizures Both hippocampi removed Unable to learn new declarative information Can learn new motor skills: golf, mirror writing

S.Seung, MIT

S.Seung, MIT

Outline Origins of the synaptic hypothesis of memory The hippocampus and the tragic case of H.M. The discovery of Long term potentiation (LTP) Associative and Hebbian LTP Spike-timing dependent plasticity (STDP) Induction and expression Long-term depression (LTD) The BCM rule

Over 5,000 citations

So it looks like synapses change in longterm ways. What next?

Outline Origins of the synaptic hypothesis of memory The hippocampus and the tragic case of H.M. The discovery of Long term potentiation (LTP) Associative and Hebbian LTP Spike-timing dependent plasticity (STDP) Induction and expression Long-term depression (LTD) The BCM rule

Learning Meat Bell Meat, Bell Saliva Saliva

Learning Meat Bell Bell Saliva Saliva

A post-synaptic potential (psp)

An action potential (spike)

Typical LTP protocol

Associative properties, like Aristotle and James suggested

As Hebb predicted!

Just as Hebb suggested

Sensitive to temporal contiguity, like Pavlov observed

Outline Origins of the synaptic hypothesis of memory The hippocampus and the tragic case of H.M. The discovery of Long term potentiation (LTP) Associative and Hebbian LTP Spike-timing dependent plasticity (STDP) Induction and expression Long-term depression (LTD) The BCM rule

LTP can be temporally very precise Bi and Poo, 1998

Why is STDP important?

Why is STDP important?

Synaptic strength Why is STDP important? time Fire early -> get stronger -> fire earlier Fire late -> get weaker -> fire later

Why is STDP important?

Outline Origins of the synaptic hypothesis of memory The hippocampus and the tragic case of H.M. The discovery of Long term potentiation (LTP) Associative and Hebbian LTP Spike-timing dependent plasticity (STDP) Induction and expression Long-term depression (LTD) The BCM rule

Mechanisms of expression

Outline Origins of the synaptic hypothesis of memory The hippocampus and the tragic case of H.M. The discovery of Long term potentiation (LTP) Associative and Hebbian LTP Spike-timing dependent plasticity (STDP) Induction and expression Long-term depression (LTD) The BCM rule

Long-term depression (LTD)

Outline Origins of the synaptic hypothesis of memory The hippocampus and the tragic case of H.M. The discovery of Long term potentiation (LTP) Associative and Hebbian LTP Spike-timing dependent plasticity (STDP) Induction and expression Long-term depression (LTD) The BCM rule

High frequency LTP

Low frequency LTD

Test pulse at 0.067 Hz: no change

Synaptic change (%) The BCM theory of synaptic plasticity + 0.1 1 10 100 Frequency (Hz) -

BCM predicts a leftward shift for lower spontaneous activity % = Light reared = Dark reared

BCM predicted the data % = Light reared = Dark reared A new type of LTP

Timing induced LTP

Timing induced LTD

Unresolved issues Asymmetry of induction: 120 vs. 900 pulses What causes the shape of the BCM curve? Frequency results did not predict timing results Timing results do not say why 1 Hz unpaired induces LTD, yet 0.1 Hz unpaired induces no change