Figure 5.

a, NMDA spikes can be elicited without AMPA current. With all AMPA conductance inactivated (as in a CNQX experiment in slice), NMDA spikes could still be produced. In this example, in 2 mm [Mg²⁺], synaptic input was distributed over an entire 65 μm end-segment (indicated by the location of the dendritic electrode in the image inset), with normal threshold ∼45 nS total NMDA conductance. Absent all synaptic AMPA current, the NMDA spike still occurred. The three somatic traces (black) represent 65, 70, and 75 nS total NMDA conductance applied and distributed evenly across the 65 μm segment. Thus, without AMPA to assist in reaching local threshold, the amount of NMDA conductance required to elicit the NMDA spike increased to ∼70 nS, suggesting that although the AMPA current does not drive the NMDA spike, it assists in its initiation. A further increase in AMPA did not decrease the NMDA conductance threshold, reflecting the observation that AMPA did not participate in driving the NMDA spike once it was initiated. b, The shape of the NMDA spike. To examine whether high levels of AMPA could substitute in part for NMDA conductance to produce an event resembling an NMDA spike, sufficient AMPA conductance was applied to a basal branch so that the EPSP amplitude in the soma was that of a large NMDA event (right, top trace; same stimulation and dendritic recording location as in Figure 4a). In the paired-pulse protocol, the resulting EPSP shapes were compared with those in a simulated event in which synaptic NMDA conductance predominated (below). An overlay with a recorded NMDA spike (green trace; courtesy of J. Schiller) was made in both cases; the time scales of the simulated and recorded events are the same, although the amplitude scale of the recorded event was adjusted slightly to normalize peak amplitude to facilitate the comparison of shape. Clearly, the shape of recorded paired-pulse responses are more consistent with simulated events in which NMDA is the dominant synaptic current. The ratio of amplitude of the first and second pulse observed experimentally (∼1:5) is not consistent with an AMPA-dominated event. The comparison of shape as well as relative amplitude of the elicited EPSPs suggests that AMPA is a relatively small component of the currents driving the NMDA spike (see Discussion).