Apical tuft input efficacy in layer 5 pyramidal cells from rat visual cortex

I. The integration of synaptic inputs to the apical dendrite of layer 5 neo cortical pyramidal cells was studied using compartment model simulations. T he goal was to characterize the generation of regenerative responses to syn aptic inputs under two conditions: (a) where there was an absence of backgr ound synaptic input, and (b) when the entire cell surface was subjected to a uniform blanket of synaptic background conductance such that somatic inpu t resistance was reduced 5-fold. 2. Dendritic morphology corresponded to a layer 5 thick-trunked pyramidal c ell from rat primary visual cortex at postnatal day 28 (P28), with distribu tion of dendritic active currents guided by the electrophysiological charac teristics of the apical trunk reported in this cell type. Response characte ristics for two dendritic channel distributions were compared, one of which supported Ca2+ spikes in the apical dendrite. 3. In the absence of background, synaptic input, to the apical tuft was sur prisingly effective in eliciting somatic firing when compared with input to apical oblique branches. This result obtained even when the tuft membrane was the least excitable in the dendritic tree. 4. The special efficacy of tuft input arose because its electrotonic charac teristics favour development of a sustained depolarization which charged th e apex of the apical trunk to its firing threshold; once initiated in the d istal trunk, firing propagated inward to the soma. This mechanism did not d epend upon the presence of depolarizing channels in tuft membrane, but did require an excitable apical trunk. 5. Rather than disconnect the tuft, background synaptic conductance enhance d the efficacy advantage enjoyed by input arriving there. This counterintui tive result arose because background reduced the subthreshold spread of vol tage, and so diminished the ability of the excitation of various individual oblique branches to combine to charge the relatively thick adjacent trunk. In contrast, drive from the depolarized tuft is exerted at a single critic al point, the apex of the distal trunk, and so was relatively undiminished by the background. Further, once initiation at the apex occurred, backgroun d had little effect oil inward propagation along the trunk. 6. We conclude that synaptic input to the apical tuft of layer 5 cells may be unexpectedly effective in triggering cell firing itt rim. The advantage in efficacy was not dependent upon the characteristics of tuft membrane exc itability, but rather stemmed from the geometry of the tuft, and its juncti on with the distal apical trunk. The efficacy of tuft input wa,,, howe,er, critically dependent upon inward propagation, suggesting that modulation of membrane currents which affect propagation in the apical trunk might sensi tively control the efficacy of tuft input.