Beyond Vanilla LTP

Spike-timing-dependent-plasticityor

STDP

Hebbian learning rule

aSN MNWMN,aSN

Δwij = μ xj (vi - φ) learning threshold under which LTD can occur

Stimulation electrodeR di l d ( ll l )Recording electrode (extracellular)

Recording electrode (intracellular)

100%

Baseline

5 sec

100 Hz tetanus

... 2 hours

Tetanustetanus

postsynaptic activation > threshold to increase wij

Δwij = μ xj (vi - φ)

Recording electrode (extracellular)

Recording electrode (intracellular)

5 sec

... 2 hours

100%

Baseline 20 Hz 20 Hz

postsynaptic activation < threshold to decrease wij

Δwij = μ xj (vi - φ)

vivi

xj

time

Δwij = μ * xj * (vi-φ) time100 Hz

vi

xj

time

itime20 Hz

vi

xj

time

time10 Hz10 Hz

Induction of LTP or LTD depends not only on firing frequency butInduction of LTP or LTD depends not only on firing frequency but also on precise temporal relationship between the pre- and postsynaptic action potentials.

Paired

PrePost

Paired

Pre or post only

tpost - tpre = 5ms

Paired

PrePost

Paired

Pre or post only

tpost - tpre = 5ms

Paired

PrePost

Paired

Pre or post only

Baseline

tpost - tpre = 5ms

Repeated pairing (20x)

Pre Post

Paired

pre-onlypost-only

Experimental manipulation

pre and post AP's separated by 5 ms

pre

post10x

< 20 Hz: no LTP> 20 Hz: more LTP

pre20 Hz 20 Hz

4 seconds

Markram et al Regulation of synaptic efficacy by coincidence ofpostsynaptic APs and EPSPsMarkram et al. Regulation of synaptic efficacy by coincidence ofpostsynaptic APs and EPSPs.Science. 1997 Jan 10;275(5297):213-5.

1. Stimulate cell1: > burst of action potentials in cell1

(1) Lets assume a burst of action potentialsis first evoked in cell 1. This burst of action

cell 1 cell 2-> burst of action potentials in cell1-> EPSPs in cell2

potentials will evoke an EPSP in cell 2.

(2)Subsequently a burst of action potentials is evoked in cell 2, which will evoke and EPSP in cell 1.

(1)(2)

In the example shown here, (1) and (2) are separatedby 100 ms. Because the cells are reciprocally connected, in each cell, the burst of action potentials and evoked EPSPs are separated by 100ms. In cell 1, the burst of action potentials precceeds the EPSP by

(1)

(2)

Bursts of AP triggered 10 ms

p p y100 ms and in cell 2, the EPSP preceeds the actionpotentials by 100 ms.

(2)

apart

1. Stimulate cell1: > burst of action potentials in cell1

(1) Lets assume a burst of action potentialsis first evoked in cell 1. This burst of action

cell 1 cell 2-> burst of action potentials in cell1-> EPSPs in cell2

potentials will evoke an EPSP in cell 2.

(2)Subsequently a burst of action potentials is evoked in cell 2, which will evoke and EPSP in cell 1.

(1)(2)

2. Stimulate cell2: -> burst of action potentials in cell2-> EPSPs in cell1

In the example shown here, (1) and (2) are separatedby 100 ms. Because the cells are reciprocally connected, in each cell, the burst of action potentials and evoked EPSPs are separated by 100ms. In cell 1, the burst of action potentials precceeds the EPSP by

(1)

(2)

Bursts of AP triggered 10 ms

p p y100 ms and in cell 2, the EPSP preceeds the actionpotentials by 100 ms.

(2)

apart

1. Stimulate cell1: > burst of action potentials in cell1

(1) Lets assume a burst of action potentialsis first evoked in cell 1. This burst of action

cell 1 cell 2-> burst of action potentials in cell1-> EPSPs in cell2

potentials will evoke an EPSP in cell 2.

(2)Subsequently a burst of action potentials is evoked in cell 2, which will evoke and EPSP in cell 1.

(1)(2)

2. Stimulate cell2: -> burst of action potentials in cell2-> EPSPs in cell1

In the example shown here, (1) and (2) are separatedby 100 ms. Because the cells are reciprocally connected, in each cell, the burst of action potentials and evoked EPSPs are separated by 100ms. In cell 1, the burst of action potentials precceeds the EPSP by

(1)

(2)

Cell1: APs 100ms before EPSPs

Bursts of AP triggered 10 ms

p p y100 ms and in cell 2, the EPSP preceeds the actionpotentials by 100 ms.

(2) Cell2: EPSPs 100ms before APs

apart

1. Stimulate cell1: > burst of action potentials in cell1

(1) Lets assume a burst of action potentialsis first evoked in cell 1. This burst of action

cell 1 cell 2-> burst of action potentials in cell1-> EPSPs in cell2

potentials will evoke an EPSP in cell 2.

(2)Subsequently a burst of action potentials is evoked in cell 2, which will evoke and EPSP in cell 1.

(1)(2)

2. Stimulate cell2: -> burst of action potentials in cell2-> EPSPs in cell1

In the example shown here, (1) and (2) are separatedby 100 ms. Because the cells are reciprocally connected, in each cell, the burst of action potentials and evoked EPSPs are separated by 100ms. In cell 1, the burst of action potentials precceeds the EPSP by

(1)

(2)

Cell1: APs 100ms before EPSPs

Bursts of AP triggered 10 ms

p p y100 ms and in cell 2, the EPSP preceeds the actionpotentials by 100 ms.

(2) Cell2: EPSPs 100ms before APs

EPSP : input from presynaptic cellapart

EPSP : input from presynaptic cellAP: output from postsynaptic cell

EPSP followed by AP: pre before post: tpre - tpost < 0y p p pre postAP followed by EPSP: post before pre: tpre - tpost > 0

cell 1 cell 2

Strengtheningof synaptic strength was obtainedh th t t ll fi d 10 ft it EPSPAP before EPSP: weakening

when the postsynaptc cell fired 10 ms after its EPSP

Weakening of synaptic strength was obtained when the postsynaptic cell fired 10 ms before its EPSP

No change in synaptic strength was obtained when the

of synaptic strength

EPSP before AP: strengthening

Bursts of AP triggered 100 ms apart Bursts of AP triggered 10 ms

No change in synaptic strength was obtained when the postsynaptic EPSP and AP were separated by 100ms in either direction.

EPSP before AP: strengthening of synaptic strength

Bursts of AP triggered 100 ms apart Bursts of AP triggered 10 ms apart

Summary:Summary:

1) If a pre-synaptic cell fires BEFORE a connected postsynaptic cell, the synapse connecting them increases in strength

2) If pre-synaptic cell fires AFTER a connected postsynaptic cell, the synpase between them decreases in strength

t tpre post

pre

pre post

pre p

post

p

post

Consider our previous example on classical conditioning: p p g

Sensory input

Motor output

Food

F

S

Mpre before post

The change in EPSC (exitatory postsynapticThe change in EPSC (exitatory postsynapticcurrent) is plotted as a function of the time elapsed between the postsynaptic actionpotential and the the postsynaptic EPSP duringsimultaneous stimulation of pre- and postsynaptic

llcells.

Bi, GQ and Poo, MM. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.J Neurosci. 1998 Dec 15;18(24):10464-72.

b f tpre before post

post before pre

Δt = timepre - timepost

Bi, GQ and Poo, MM. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing synaptic Song Miller and Abbott Competitive Hebbianhippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.J Neurosci. 1998 Dec 15;18(24):10464-72.

Song, Miller and Abbott, Competitive Hebbian learning through spike-timing-dependent synaptic plasticity.Nat Neurosci. 2000 Sep;3(9):919-26.

Δw

pre

post

5 ms 20 ms

.

. N

1

.

N presynaptic spike trainsN synaptic weight

.

. N

1

.

N presynaptic spike trainsN synaptic weight

leaky integrate and fire current due to excitatory inputs

current due to excitatory inputs

[τ dv/dt = -v + inputs]

excitatory inputs excitatory inputs

When Vm >= -54 mV

.

. N

1 When Vm >= -54 mV, neuron fires and Vm = -70 mV

.

N presynaptic spike trainsN synaptic weight

leaky integrate and fire current due to excitatory inputs

current due to excitatory inputsexcitatory inputs excitatory inputs

Vrest = -70 mV, Eex = 0 mV; Ein = -70 mV

postsynaptic spikestra

ins

naps

es .. N

napt

ic sp

ike

syn .

N presynaptic spike trains

pres

yn

time weights

postsynaptic spikes

pre before post

b f

train

s

naps

es .. N

Δt = timepre - timepost

post before pre

napt

ic sp

ike

syn .

N presynaptic spike trains

pres

yn

time weights

NO LEARNING: A+ = 0 and A- = 0

A+ >0 and A- = 0 A+ =0 and A- > 0

A+ ~= A- A+ < A-

Stabilizes Hebbian learningIntroduces competition Favors synchronous presynaptic events

Δt = time - time tΔt timepre timepost

Issues:

At high firing rates, when pre and postsynaptic neuronsare phase-locked both parts of the learning ruleare phase locked, both parts of the learning rule apply for any given spike!

20 ms (50 Hz)

pre

30 mspost

10 ms

Issues:

At high firing rates, when pre and postsynaptic neuronsare phase-locked, both parts of the learning rule apply for any given spike! pp y y g p

20 ms (50 Hz)

pre

post+

++

+ --

postsynaptic spikes interacts with eachpostsynaptic spikes interacts with each presynaptic spike and effects sum up linearly!

Issues:

At high firing rates, when pre and postsynaptic neuronsare phase-locked, both parts of the learning rule apply for any given spike! pp y y g p

20 ms (50 Hz)

pre

post++ -

postsynaptic spikes interacts only withpostsynaptic spikes interacts only withimmediatly preceeding presynaptic spikes

Here we have systematically varied the rate, timing and number of coincident afferents in order to explore the rules that govern induction of long-term plasticity b t ti ll t d thi k t ft d L5 i t i l tbetween monosynaptically connected thick, tufted L5 neurons in rat visual cortex. Our experiments reveal a joint dependence of plasticity on timing and rate, as well as a novel form of cooperativity operating even when the postsynaptic AP is evoked by current injection Based on these experiments we have constructed aevoked by current injection. Based on these experiments we have constructed a quantitative description, which accurately predicts the build-up of potentiation and depression during random firing.

Sjostrom PJ, Turrigiano GG, and Nelson SB. Rate, timing, and cooperativityjointly determine cortical synaptic plasticity. Neuron 32: 1149-1164, 2001.

presynaptic

t tipostsynaptic

measure for strength of synapse

1) LTP depends on stimulation frequency

40 Hz 0.1 Hz

1) LTP depends on stimulation frequency

40 Hz 0.1 Hz

1) LTP depends on stimulation frequency

40 Hz 0.1 Hz

At high frequencies, LTP always dominates!

At high frequencies, LTP always dominates!

All spike interactions

li l

Only nearest spike

All spike interactions sum linearly, but if LTP

sum linearly spike interactions count

y,is present, LTD is not applied

All three models used frequency and voltage dependencies determinedfrom data in this paper.

Models tested with new data NOT used for fitting!