Human cortical pyramidal neurons: From spines to spikes via models

Eyal, G.; Verhoog, M. B.; Testa-Silva, G.; Deitcher, Y.; Benavides-Piccione, R.; DeFelipe, J.; de Kock, C. P. J.; Mansvelder, H. D.; Segev, I.

doi:10.1101/267898

bioRxiv · 10.1101/267898

Human cortical pyramidal neurons: From spines to spikes via models

Eyal, G.·Verhoog, M. B.·Testa-Silva, G.·Deitcher, Y.·Benavides-Piccione, R.·DeFelipe, J.·de Kock, C. P. J.·Mansvelder, H. D.·Segev, I.

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Abstract

We present the first-ever 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 post mortem tissues from human temporal cortex. The models predicted particularly large AMPA- and NMDA- conductances per synaptic contact (0.88 nS and 1.31nS, 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. 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 M{Omega}). 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 temporal cortex. These multi-sites nonlinear 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.

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Eyal, G., Verhoog, M. B., Testa-Silva, G., Deitcher, Y., Benavides-Piccione, R., DeFelipe, J., de Kock, C. P. J., Mansvelder, H. D., Segev, I.. 2018-02-19. Human cortical pyramidal neurons: From spines to spikes via models. https://doi.org/10.1101/267898

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