Summation of AMPA-mediated EPSPs in rat neocortical pyramidal neurons

Abstract

It has been hypothesized that voltage-sensitive conductances present on the dendrites of neurons can influence the summation of EPSPs and hence affect how neurons compile information. Greater than linear summation of EPSPs has been postulated to facilitate coincidence detection by cortical neurons. This study examined whether the summation of subthreshold AMPA-mediated EPSPs generated on layer V neocortical pyramidal neurons in vitro was linear or nonlinear, and if any nonlinearities could be attributed to dendritic conductances. Evoked EPSPs (1--12 mV) were recorded somatically by means of intracellular sharp electrodes in the presence of 100 muM AP-5 and 3 muM bicuculline. Two independent EPSPs were evoked by two stimulating electrodes, one in layer I and another in layers III--V. The areas of stimulation were isolated from each other by a horizontal cut below layer I. To block post-synaptic conductances (i.e. Na+, Ca2+) in a subset of neurons, 50 mM QX-314 was included in the recording electrode. The presence of QX-314 in the electrodes significantly decreased the amount of superlinear summation compared to control conditions. With KCl electrodes, but not QX-314 electrodes, EPSP summation was affected by changes in postsynaptic membrane potential. Superlinear summation of EPSPs decreased as the time between stimuli decreased only when using KCl electrodes. To determine the role of dendrites play in non-linear summation, a current pulse (simulated EPSP) delivered at the soma was substituted for either or both of the proximally and distally evoked EPSPs. Simulated EPSPs combined with either an evoked EPSP or another simulated EPSP showed significantly less superlinear summation then two evoked EPSPs, indicating that the dendritic conductances are largely responsible for the observed superlinear summation.