Figure 9.

a, A 35 ms time window for inhibitory suppression of an NMDA spike. To examine the degree of temporal coincidence required for inhibition to be effective in suppressing an NMDA spike, the latency of inhibition relative to arrival of excitation was varied from −30 to +30 ms. Arrival time of inhibitory conductance is indicated by the blue arrowheads, with earliest latencies represented by the lightest shades of gray. The excitatory and inhibitory conductance magnitudes (2 nS AMPA, 8 nS NMDA, and 2 nS GABA, respectively; in 1 mm [Mg²⁺]) were as in Figure 8b, with the inhibitory conductance applied 23 μm proximal to the excitation (blue pipette in inset). Inhibitory input arriving up to 20–25 ms before the excitation, a time period that is sensitive to the time course of the inhibitory conductance (see Materials and Methods), was effective in preventing the NMDA spike at these conductance magnitudes. Inhibition arriving 5–10 ms after the arrival of excitation abruptly quenched the NMDA spike ongoing, curtailing its impact. Thus, with these parameters, a 35 ms window existed in time, most of which precedes excitation, during which targeted dendritic inhibition effectively suppressed the triggering of an NMDA spike. b, c, Inhibition is most effective in suppressing NMDA spikes when targeted to the distal tip. To ascertain whether the colocalization of inhibition with excitation was necessary for its effectiveness, the same paradigm as a was used but with the inhibition applied within the same tertiary branch, but either more proximal or distal to the location of excitatory conductance. Locations of inhibition (blue pipette) and excitation (gray pipette) are as shown in inset. Surprisingly, inhibition at the proximal end (b), near the bifurcation, was relatively ineffective in curtailing the NMDA spike, regardless of latency. In contrast, inhibition applied to the distal-most tip (c) was at least as effective as when it was colocalized with excitation.