Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo

During wakefulness, neocortical neurons are subjected to an intense synapti c bombardment. To assess the consequences of this background activity for t he integrative properties of pyramidal neurons, we constrained biophysical models with in vivo intracellular data obtained in anesthetized cats during periods of intense network activity similar to that observed in the waking state. In pyramidal cells of the parietal cortex (area 5-7), synaptic acti vity was responsible for an approximately fivefold decrease in input resist ance (R-in), a more depolarized membrane potential (V-m), and a marked incr ease in the amplitude of V-m fluctuations, as determined by comparing the s ame cells before and after microperfusion of tetrodotoxin (TTX). The model was constrained by measurements of R-in, by the average value and standard deviation of the V-m measured from epochs of intense synaptic activity reco rded with KAc or KCl-filled pipettes as well as the values measured in the same cells after TTX. To reproduce all experimental results, the simulated synaptic activity had to be of relatively high frequency (1-5 Hz) at excita tory and inhibitory synapses. In addition, synaptic inputs had to be signif icantly correlated (correlation coefficient similar to 0.1) to reproduce th e amplitude of V-m fluctuations recorded experimentally. The presence of vo ltage-dependent K+ currents, estimated from current-voltage relations after TTX, affected these parameters by <10%. The model predicts that the conduc tance due to synaptic activity is 7-30 times larger than the somatic leak c onductance to be consistent with the approximately fivefold change in R-in. The impact of this massive increase in conductance on dendritic attenuatio n was investigated for passive neurons and neurons with voltage-dependent N a+/K+ currents in soma and dendrites. In passive neurons, correlated synapt ic bombardment had a major influence on dendritic attenuation. The electrot onic attenuation of simulated synaptic inputs was enhanced greatly in the p resence of synaptic bombardment, with distal synapses having minimal effect s at the soma. Similarly, in the presence of dendritic voltage-dependent cu rrents, the convergence of hundreds of synaptic inputs was required to evok e action potentials reliably. In this case, however, dendritic voltage-depe ndent currents minimized the variability due to input location, with distal apical synapses being as effective as synapses on basal dendrites. In conc lusion, this combination of intracellular and computational data suggests t hat, during low-amplitude fast electroencephalographic activity: neocortica l neurons are bombarded continuously by correlated synaptic inputs at high frequency, which significantly affect their integrative properties. A serie s of predictions are suggested to test this model.