Figure 1: Noncanonical STDP induction rules at CA3–CA3 recurrent synapses.

(a) Neurolucida reconstruction of a representative CA3 pyramidal neuron filled with biocytin. Inset shows AP phenotype (1-s current pulse, 630 pA); recording and stimulation pipettes are indicated schematically. Blue, soma and dendrites; red, axon; sp, stratum pyramidale; so, stratum oriens. (b,c) Pre–postsynaptic pairing induces LTP at CA3–CA3 recurrent synapses. Plot of compound EPSP peak amplitude against experimental time before and after pre–postsynaptic pairing (Δt=+10 ms; vertical grey bars). Single-cell data (b) and mean data (c; 9 cells). (d,e) Post–presynaptic pairing also induces LTP. Similar plot as in b, c, but for post–presynaptic pairing (with Δt=–10 ms). Single-cell data (d) and mean data (e; 17 cells). Insets in b and d show the average of 60 evoked EPSPs before (black) and 20–30 min after induction (grey). Scale bar in b also applies in d. In c and e, EPSP amplitude was normalized to the control value before LTP induction (dashed line). (f,g) Multiple Ca2+ sources were necessary for STDP induction. Summary bar graph shows the effects of 20 μM of the NMDA receptor antagonist D-AP5 (extracellular; 7 and 6 cells), 20 mM of the Ca2+ chelator EGTA (intracellular; 8 and 6 cells) and 10 μM of the L-type Ca2+ channel blocker nimodipine (extracellular; 5 and 5 cells, respectively) on pairing-induced LTP for pre–postsynaptic (f) and post–presynaptic sequences (g). Circles represent data from individual cells, bars indicate mean±s.e.m. LTP with both pairing paradigms was largely abolished by all manipulations. (h,i) A broad and symmetric STDP curve at CA3–CA3 synapses. Magnitude of potentiation induced by pre–postsynaptic and post–presynaptic pairing was plotted against pairing time interval Δt. Representative average traces are shown in h (grey, before induction; black, 20–30 min after induction), plot of LTP magnitude (expressed as % increase over baseline) against Δt is shown in i (69 cells total). Red curve, Gaussian function without offset fit to the data points. *, P<0.05; **, P<0.01; ***, P<0.001.