Modulation of EPSP shape and efficacy by intrinsic membrane conductances in rat neocortical pyramidal neurons in vitro.

1. Intracellular recordings were made from pyramidal neurons in layers II/III and V of rat visual cortical slices. Distal and proximal excitatory postsynaptic potentials (EPSPs) were evoked using extracellular bipolar electrodes placed on the slice horizontal to each cell, near the apical and basal dendrites respectively. Experiments were conducted in the presence of 2-amino-5-phosphonopentanoate, picrotoxin and, in most cases, 2-hydroxy-saclofen. 2. For layer II/III pyramidal neurons, voltage undershoots following distal and proximal EPSPs (n = 7 pairs) and injected somatic pulses were rarely apparent. In layer V pyramidal neurons substantial voltage undershoots were recorded following distal and proximal EPSPs (n = 27 pairs) and injected somatic pulses, with undershoot being greatest for apical inputs (P = 0.001). The greater undershoots following apical EPSPs were also apparent in semilogarithmic plots of voltage decay where the slope of decay for apical EPSPs was quicker than the voltage decay following pulses of current injected at the soma. There was no significant difference in the shapes of distal and proximal EPSPs in layer II/III or layer V pyramidal cells under control conditions. 3. Pharmacological agents were used to reduce voltage undershoots. The most successful of these was alinidine, a putative blocker of the slow inward rectifier (IH) conductance. In the presence of bath-applied 100 microM alinidine, undershoots were significantly reduced and it became possible to distinguish the relative origins of EPSPs on the basis of their shape. Distally generated EPSPs (n = 14) had rise times and half-widths that were 2.8 and 1.5 times longer respectively than those evoked proximally (n = 10; P = 0.001 for both parameters). 4. These results confirm previous theoretical simulations of somatic recordings in passive model neurons where distal EPSPs display slower rise times and longer half-widths than proximal EPSPs. The present results suggest that, at least in pyramidal neurons of layer V, distal synaptic inputs can be specifically modulated by intrinsic membrane conductances.