The supralinear response evoked at CA3 recurrent synapses is mediated by an NMDA spike. (A) Image of a CA3 pyramidal cell during recording from the proximal apical dendrite. (Scale bar: 15 μm.) (B) A current-clamp recording from the apical dendrite (158 μm from the soma) in control conditions (before repetitive pairing) showing a supralinear summation of CA3 and mossy fiber-evoked responses. Traces are averages of 10 sweeps. The first two traces show averaged EPSPs evoked by a CA3 input and by a mossy fiber input alone. When mossy fiber stimulation follows CA3 stimulation with a delay of 10 ms, a supralinear response can be evoked. All traces with +10-ms pairings are scaled to the mean single-pulse CA3 EPSP. Supralinear summation is prevented by an NMDA receptor antagonist or by clamping the cell at −90 mV. (C) The timing of inputs is critical for induction of supralinear responses. A supralinear response is generated when a CA3 recurrent response is followed after 10 ms by a mossy fiber response, as in our LTP protocol (dendritic recording: 172 μm from the soma). Synchronous stimulation or a mossy fiber response preceding a CA3 recurrent response by 35 ms (as in the LTD protocol) does not produce a supralinear response. (D) Simultaneous recording from a first-order apical dendritic branch (upper traces) and from the soma (lower traces) showing averaged traces of a CA3 recurrent EPSP, a mossy fiber EPSP, a paired linear response, and a paired supralinear response. The greater amplitude of the signals in the dendritic recording indicates that for this cell, the synapses stimulated by the CA3 recurrent input are close to the recorded dendritic branch but far from the soma. In these cases, the supralinear response is greater (less attenuated) in the dendritic recording compared with the somatic recording. (E) In contrast, in cases where the stimulated CA3 recurrent input induces a smaller EPSP in the recorded dendrite than in the soma (dashed lines), the measured supralinearity is smaller in the dendritic recording than in the somatic recording. (F) Consequently, the magnitude of the supralinear responses recorded in the dendrite increases as a function of the ratio of the amplitude of the dendritic/somatic CA3 recurrent EPSP.