Human cortical pyramidal neurons: From spines to spikes via models

Guy Eyal, Matthijs B. Verhoog, Guilherme Testa-Silva, Yair Deitcher, Ruth Benavides Piccione, Javier DeFelipe, Christiaan P.J. de Kock, Huibert D. Mansvelder, Idan Segev

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

We present detailed models of pyramidal cells from human neocortex, including models on their excitatory synapses, dendritic spines, dendritic NMDA- and somatic/axonal Na+ spikes that provided new insights into signal processing and computational capabilities of these principal cells. Six human layer 2 and layer 3 pyramidal cells (HL2/L3 PCs) were modeled, integrating detailed anatomical and physiological data from both fresh and postmortem tissues from human temporal cortex. The models predicted particularly large AMPA- and NMDA-conductances per synaptic contact (0.88 and 1.31 nS, respectively) and a steep dependence of the NMDA-conductance on voltage. These estimates were based on intracellular recordings from synaptically-connected HL2/L3 pairs, combined with extra-cellular current injections and use of synaptic blockers, and the assumption of five contacts per synaptic connection. A large dataset of high-resolution reconstructed HL2/L3 dendritic spines provided estimates for the EPSPs at the spine head (12.7 ± 4.6 mV), spine base (9.7 ± 5.0 mV), and soma (0.3 ± 0.1 mV), and for the spine neck resistance (50–80 MΩ). Matching the shape and firing pattern of experimental somatic Na+-spikes provided estimates for the density of the somatic/axonal excitable membrane ion channels, predicting that 134 ± 28 simultaneously activated HL2/L3-HL2/L3 synapses are required for generating (with 50% probability) a somatic Na+ spike. Dendritic NMDA spikes were triggered in the model when 20 ± 10 excitatory spinous synapses were simultaneously activated on individual dendritic branches. The particularly large number of basal dendrites in HL2/L3 PCs and the distinctive cable elongation of their terminals imply that ~25 NMDA-spikes could be generated independently and simultaneously in these cells, as compared to ~14 in L2/3 PCs from the rat somatosensory cortex. These multi-sites non-linear signals, together with the large (~30,000) excitatory synapses/cell, equip human L2/L3 PCs with enhanced computational capabilities. Our study provides the most comprehensive model of any human neuron to-date demonstrating the biophysical and computational distinctiveness of human cortical neurons.

Original languageEnglish
Article number181
Pages (from-to)1-24
Number of pages24
JournalFrontiers in Cellular Neuroscience
Volume12
Issue numberJune
DOIs
Publication statusPublished - 29 Jun 2018

Fingerprint

Pyramidal Cells
Spine
N-Methylaspartate
Synapses
Dendritic Spines
Ion Channels
Neurons
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Somatosensory Cortex
Excitatory Postsynaptic Potentials
Neocortex
Carisoprodol
Temporal Lobe
Dendrites
Injections

Keywords

  • Compartmental modeling
  • Cortical excitatory synapses
  • Dendritic spines
  • Human pyramidal cells
  • Multi objective optimization
  • Neuron computation
  • Non-linear dendrites

Cite this

Eyal, G., Verhoog, M. B., Testa-Silva, G., Deitcher, Y., Piccione, R. B., DeFelipe, J., ... Segev, I. (2018). Human cortical pyramidal neurons: From spines to spikes via models. Frontiers in Cellular Neuroscience, 12(June), 1-24. [181]. https://doi.org/10.3389/fncel.2018.00181
Eyal, Guy ; Verhoog, Matthijs B. ; Testa-Silva, Guilherme ; Deitcher, Yair ; Piccione, Ruth Benavides ; DeFelipe, Javier ; de Kock, Christiaan P.J. ; Mansvelder, Huibert D. ; Segev, Idan. / Human cortical pyramidal neurons : From spines to spikes via models. In: Frontiers in Cellular Neuroscience. 2018 ; Vol. 12, No. June. pp. 1-24.
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Human cortical pyramidal neurons : From spines to spikes via models. / Eyal, Guy; Verhoog, Matthijs B.; Testa-Silva, Guilherme; Deitcher, Yair; Piccione, Ruth Benavides; DeFelipe, Javier; de Kock, Christiaan P.J.; Mansvelder, Huibert D.; Segev, Idan.

In: Frontiers in Cellular Neuroscience, Vol. 12, No. June, 181, 29.06.2018, p. 1-24.

Research output: Contribution to JournalArticleAcademicpeer-review

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Eyal G, Verhoog MB, Testa-Silva G, Deitcher Y, Piccione RB, DeFelipe J et al. Human cortical pyramidal neurons: From spines to spikes via models. Frontiers in Cellular Neuroscience. 2018 Jun 29;12(June):1-24. 181. https://doi.org/10.3389/fncel.2018.00181