Figure 4.

a, Threshold for NMDA spike generation was much higher in proximal branches. In this example, in 2 mm [Mg²⁺] and with a 25 ms paired-pulse interval, nearly 40 nS of NMDA was required to produce an NMDA event. The greater threshold correlated with the lower input impedance of the more proximal branch. Here, AMPA conductance was 3 nS. Larger AMPA conductance values increased the EPSP amplitude of the first EPSP but did not reduce the level of NMDA conductance required to trigger a regenerative event. Substantially higher levels of AMPA conductance were inconsistent with the first versus second EPSP amplitude ratio observed in paired-pulse protocols in vitro (compare Fig. 3a, left traces). The site of stimulation in this example was ∼70 μm from the soma. For stimulation at more proximal loci, an NMDA spike could not be elicited, consistent with the corresponding observations with focal extracellular stimulation in vitro (Schiller et al., 2001). b, The minimum amount of NMDA conductance required to produce an NMDA spike in 2 mm [Mg²⁺]was ∼10 nS. Synaptic conductance was applied to a 23 μm subsegment of a fine tertiary basal branch, the center of which was ∼211 μm from the cell body. These high-impedance distal tertiary segments supported the generation of an NMDA spike with the lowest threshold. The regenerative nature of the event is illustrated by the large jump in the somatic EPSP when synaptic conductance was increased incrementally from 8 to 10 nS. Once threshold was reached, the subsequent increase in NMDA conductance had a smaller effect. For all stimuli, the AMPA component of synaptic conductance was 2 nS. In all Figures and throughout the text, conductance values refer to conductance at peak, without any Mg²⁺ blockade. The threshold NMDA conductance at this location declined to ∼6 nS when external [Mg²⁺] was decreased from 2 mm (the concentration in the simulation depicted in this Figure) to 1 mm.