(A) The synaptic weight is the product of a presynaptic factor P and a postsynaptic factor q. Long-term modifications in P and q are governed by interactions between the pre- and postsynaptic spike trains. (B) Model example in which the postsynaptic neuron first spikes three times at 20 Hz (Y) Δt = +10 ms after the presynaptic neuron (X), leading to LTP by increasing both q and P. Next, when the relative timing Δt is reversed, long-term depression (LTD) results as P weakens strongly, even though q still slightly strengthens. (C) The model fits the rate dependence of synaptic plasticity (squares, (Sjöström et al., 2001)) for both positive (blue: +10 ms) and negative timings (red: −10 ms). (D, E) The changes in the pre- and postsynaptic factors P and q match experimental data (reanalyzed from Sjöström et al., 2001; see ‘Materials and methods’ and Figure 1—figure supplement 2). (F, G) As in experiments (top), short-term depression in the model is reduced after LTD (20 Hz, Δt = −10 ms) and increased after LTP (50 Hz, Δt = +10 ms) (bottom). Experimental traces from Sjöström et al. (2003) (F) and from Sjöström et al. (2007) (G). (H) Model (blue) is consistent with LTP experiments (black) (Sjöström et al., 2007) in control conditions, NO blockade, and eCB blockade. NO and eCB antagonists abolish and promote presynaptic LTP, respectively (Sjöström et al., 2007).