Passive and active shaping of unitary responses from associational/commissural and perforant path synapses in hippocampal CA3 pyramidal cells

Although associational/commissural (A/C) and perforant path (PP) inputs to CA3b pyramidal cells play a central role in hippocampal mnemonic functions, the active and passive processes that shape A/C and PP AMPA and NMDA receptor-mediated unitary EPSP/EPSC (AMPA and NMDA uEPSP/uEPSC) have not been fully characterized yet. Here we find no differences in somatic amplitude between A/C and PP for either AMPA or NMDA uEPSPs. However, larger AMPA uEPSCs were evoked from proximal than from distal A/C or PP. Given the space-clamp constraints in CA3 pyramidal cells, these voltage clamp data suggest that the location-independence of A/C and PP AMPA uEPSP amplitudes is achieved in part through the activation of voltage dependent conductances at or near the soma. Moreover, similarity in uEPSC amplitudes for distal A/C and PP points to the additional participation of unclamped active conductances. Indeed, the pharmacological blockade of voltage-dependent conductances eliminates the location-independence of these inputs. In contrast, the location-independence of A/C and PP NMDA uEPSP/uEPSC amplitudes is maintained across all conditions indicating that propagation is not affected by active membrane processes. The location-independence for A/C uEPSP amplitudes may be relevant in the recruitment of CA3 pyramidal cells by other CA3 pyramidal cells. These data also suggest that PP excitation represents a significant input to CA3 pyramidal cells. Implication of the passive data on local synaptic properties is further investigated in the companion paper with a detailed computational model.