title: Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo.
abstract: During wakefulness, neocortical neurons are subjected to an intense synaptic bombardment. To assess the consequences of this background activity for the 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 activity was responsible for an approximately fivefold decrease in input resistance (Rin), a more depolarized membrane potential (Vm), and a marked increase in the amplitude of Vm fluctuations, as determined by comparing the same cells before and after microperfusion of tetrodotoxin (TTX). The model was constrained by measurements of Rin, by the average value and standard deviation of the Vm measured from epochs of intense synaptic activity recorded 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 excitatory and inhibitory synapses. In addition, synaptic inputs had to be significantly correlated (correlation coefficient approximately 0.1) to reproduce the amplitude of Vm fluctuations recorded experimentally. The presence of voltage-dependent K+ currents, estimated from current-voltage relations after TTX, affected these parameters by <10%. The model predicts that the conductance due to synaptic activity is 7-30 times larger than the somatic leak conductance to be consistent with the approximately fivefold change in Rin. The impact of this massive increase in conductance on dendritic attenuation was investigated for passive neurons and neurons with voltage-dependent Na+/K+ currents in soma and dendrites. In passive neurons, correlated synaptic bombardment had a major influence on dendritic attenuation. The electrotonic attenuation of simulated synaptic inputs was enhanced greatly in the presence of synaptic bombardment, with distal synapses having minimal effects at the soma. Similarly, in the presence of dendritic voltage-dependent currents, the convergence of hundreds of synaptic inputs was required to evoke action potentials reliably. In this case, however, dendritic voltage-dependent currents minimized the variability due to input location, with distal apical synapses being as effective as synapses on basal dendrites. In conclusion, this combination of intracellular and computational data suggests that, during low-amplitude fast electroencephalographic activity, neocortical neurons are bombarded continuously by correlated synaptic inputs at high frequency, which significantly affect their integrative properties. A series of predictions are suggested to test this model.
authors: Laboratoire de Neurophysiologie, Département de Physiologie, Université Laval, Quebec G1K 7P4, Canada.
authors: A
authors: A
authors: Destexhe
authors: D
authors: D
authors: Paré
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001364:Awareness / Q000502:physiology; D002415:Cats; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004553:Electric Conductivity; D004569:Electroencephalography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology; D019579:Neocortex / Q000166:cytology* / Q000502:physiology; D009415:Nerve Net; D009434:Neural Pathways; D017966:Pyramidal Cells / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014991:Xylazine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D018691:Excitatory Amino Acid Antagonists; D014991:Xylazine; D013779:Tetrodotoxin; D007649:Ketamine