Beyond Vanilla LTP. Spike-timing-dependent-plasticity or STDP

Beyond Vanilla LTP Spike-timing-dependent-plasticity or STDP

Hebbian learning rule asn W MN,aSN MN Δw ij = μ x j (v i - φ) learning threshold under which LTD can occur

Stimulation electrode Recording electrode (extracellular) l Recording electrode (intracellular) 100% 5 sec Baseline 100 Hz tetanus... 2 hours Tetanus Δw ij = μ x j (v i - φ) postsynaptic activation > threshold to increase w ij

Recording electrode (extracellular) Recording electrode (intracellular) 100% 5 sec Baseline 20 Hz... 2 hours 20 Hz Δw ij = μ x j (v i - φ) postsynaptic activation < threshold to decrease w ij

v i x j 100 Hz time time Δw ij = μ * x j * (v i -φ) v i time x j 20 Hz time v i time x j 10 Hz time

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

Paired Pre Post Pre or post only t post -t pre = 5ms

Paired Pre Post Pre or post only Baseline t post -t pre = 5ms Repeated pairing (20x)

Pre Post Paired pre-only post-only Experimental manipulation pre and post AP's separated by 5 ms post 10x pre 20 Hz 20 Hz < 20 Hz: no LTP > 20 Hz: more LTP 4 seconds Markram et al Regulation of synaptic efficacy by coincidence ofpostsynaptic APs and EPSPs Markram et al. Regulation of synaptic efficacy by coincidence ofpostsynaptic APs and EPSPs. Science. 1997 Jan 10;275(5297):213-5.

(1) cell 1 cell 2 (2) 1. Stimulate cell1: -> burst of action potentials in cell1 -> EPSPs in cell2 (1) Lets assume a burst of action potentials is first evoked in cell 1. This burst of action 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 separated by 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 100 ms and in cell 2, the EPSP preceeds the action potentials by 100 ms. Bursts of AP triggered 10 ms apart

(1) cell 1 cell 2 (2) 1. Stimulate cell1: -> burst of action potentials in cell1 -> EPSPs in cell2 (1) Lets assume a burst of action potentials is first evoked in cell 1. This burst of action potentials will evoke an EPSP in cell 2. 2. Stimulate cell2: -> burst of action potentials in cell2 -> EPSPs in cell1 (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 separated by 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 100 ms and in cell 2, the EPSP preceeds the action potentials by 100 ms. Bursts of AP triggered 10 ms apart

(1) cell 1 cell 2 (2) 1. Stimulate cell1: -> burst of action potentials in cell1 -> EPSPs in cell2 (1) Lets assume a burst of action potentials is first evoked in cell 1. This burst of action potentials will evoke an EPSP in cell 2. 2. Stimulate cell2: -> burst of action potentials in cell2 -> EPSPs in cell1 (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 separated by 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 100 ms and in cell 2, the EPSP preceeds the action potentials by 100 ms. Cell1: APs 100ms before EPSPs Cell2: EPSPs 100ms before APs Bursts of AP triggered 10 ms apart

(1) cell 1 cell 2 (2) 1. Stimulate cell1: -> burst of action potentials in cell1 -> EPSPs in cell2 (1) Lets assume a burst of action potentials is first evoked in cell 1. This burst of action potentials will evoke an EPSP in cell 2. 2. Stimulate cell2: -> burst of action potentials in cell2 -> EPSPs in cell1 (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 separated by 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 100 ms and in cell 2, the EPSP preceeds the action potentials by 100 ms. Cell1: APs 100ms before EPSPs Cell2: EPSPs 100ms before APs EPSP : input from presynaptic cell AP: output from postsynaptic cell Bursts of AP triggered 10 ms apart EPSP followed by AP: pre before post: t pre -t post < 0 y p p pre post AP followed by EPSP: post before pre: t pre -t post > 0

cell 1 cell 2 AP before EPSP: weakening of synaptic strength Strengtheningof synaptic strength was obtained when the postsynaptc t cell llfired 10 ms after its EPSP Weakening of synaptic strength was obtained when the postsynaptic cell fired 10 ms before its EPSP EPSP before AP: strengthening No change in synaptic strength was obtained when the postsynaptic of synaptic EPSP strength and AP were separated by 100ms in either direction. Bursts of AP triggered 100 ms apart Bursts of AP triggered 10 ms apart

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 pre post pre post pre post pre post

Consider our previous example on classical conditioning: Sensory input Motor output Food F S M pre before post

The change in EPSC (exitatory postsynaptic current) is plotted as a function of the time elapsed between the postsynaptic action potential and the the postsynaptic EPSP during simultaneous stimulation of pre- and postsynaptic cells. 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.

pre bf before post post before pre Δt = time pre -time post 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. 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

1.. N. N presynaptic spike trains N synaptic weight

1.. N. N presynaptic spike trains N synaptic weight leaky integrate and fire [τ dv/dt = -v + inputs] current due to excitatory inputs current due to excitatory inputs

.. N. 1 When Vm >= -54 mv, neuron fires and Vm = -70 mv N presynaptic spike trains N synaptic weight leaky integrate and fire current due to excitatory inputs current due to excitatory inputs V rest = -70 mv, E ex = 0 mv; E in = -70 mv

postsynaptic spikes.. N. N presynaptic spike trains presynaptic spike trains synapses time weights

pre before post postsynaptic spikes post bf before pre trains presyn naptic spike syn napses. Δt = time pre - time. post N. N presynaptic spike trains time weights NO LEARNING: A+ = 0 and A- = 0

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

A+ ~= A- A+ < A-

Δt = time pre - time post Stabilizes Hebbian learning Introduces competition Favors synchronous presynaptic events

Issues: At high firing rates, when pre and postsynaptic neurons are phase-locked, both parts of the learning rule apply for any given spike! 20 ms (50 Hz) pre post 30 ms 10 ms

Issues: At high firing rates, when pre and postsynaptic neurons are phase-locked, both parts of the learning rule apply for any given spike! 20 ms (50 Hz) pre post + + + - - postsynaptic spikes interacts with each postsynaptic spikes interacts with each presynaptic spike and effects sum up linearly!

Issues: At high firing rates, when pre and postsynaptic neurons are phase-locked, both parts of the learning rule apply for any given spike! 20 ms (50 Hz) pre post + - postsynaptic spikes interacts only with postsynaptic spikes interacts only with immediatly 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 bt between monosynaptically connected tdthiktftdl5 thick, tufted 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 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 cooperativity jointly determine cortical synaptic plasticity. Neuron 32: 1149-1164, 2001.

presynaptic postsynaptic ti measure for strength of synapse

1) LTP depends on stimulation frequency 40 Hz 0.1 Hz

At high frequencies, LTP always dominates!

All spike interactions sum linearlyl Only nearest spike interactions count All spike interactions sum linearly, but if LTP is present, LTD is not applied All three models used frequency and voltage dependencies determined from data in this paper.

Models tested with new data NOT used for fitting!