The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow

Rosanna Migliore, Carmen A. Lupascu, Luca L. Bologna, Armando Romani, Jean Denis Courcol, Stefano Antonel, Werner A.H. Van Geit, Alex M. Thomson, Audrey Mercer, Sigrun Lange, Joanne Falck, Christian A. Rössert, Ying Shi, Olivier Hagens, Maurizio Pezzoli, T. Freund, Szabolcs Kali, Eilif B. Muller, Felix Schürmann, Henry MarkramMichele Migliore

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Every neuron is part of a network, exerting its function by transforming multiple spatiotemporal synaptic input patterns into a single spiking output. This function is specified by the particular shape and passive electrical properties of the neuronal membrane, and the composition and spatial distribution of ion channels across its processes. For a variety of physiological or pathological reasons, the intrinsic input/output function may change during a neuron’s lifetime. This process results in high variability in the peak specific conductance of ion channels in individual neurons. The mechanisms responsible for this variability are not well understood, although there are clear indications from experiments and modeling that degeneracy and correlation among multiple channels may be involved. Here, we studied this issue in biophysical models of hippocampal CA1 pyramidal neurons and interneurons. Using a unified data-driven simulation workflow and starting from a set of experimental recordings and morphological reconstructions obtained from rats, we built and analyzed several ensembles of morphologically and biophysically accurate single cell models with intrinsic electrophysiological properties consistent with experimental findings. The results suggest that the set of conductances expressed in any given hippocampal neuron may be considered as belonging to two groups: one subset is responsible for the major characteristics of the firing behavior in each population and the other is responsible for a robust degeneracy. Analysis of the model neurons suggests several experimentally testable predictions related to the combination and relative proportion of the different conductances that should be expressed on the membrane of different types of neurons for them to fulfill their role in the hippocampus circuitry.

Original languageEnglish
Article numbere1006423
JournalPLoS Computational Biology
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 1 2018

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Workflow
Pyramidal Cells
interneurons
Interneurons
Data-driven
Work Flow
Neurons
Data structures
Neuron
neurons
Cell
Modeling
membrane
modeling
Conductance
electrical property
ion
cells
Ion Channels
ion channels

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modelling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Cite this

The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow. / Migliore, Rosanna; Lupascu, Carmen A.; Bologna, Luca L.; Romani, Armando; Courcol, Jean Denis; Antonel, Stefano; Van Geit, Werner A.H.; Thomson, Alex M.; Mercer, Audrey; Lange, Sigrun; Falck, Joanne; Rössert, Christian A.; Shi, Ying; Hagens, Olivier; Pezzoli, Maurizio; Freund, T.; Kali, Szabolcs; Muller, Eilif B.; Schürmann, Felix; Markram, Henry; Migliore, Michele.

In: PLoS Computational Biology, Vol. 14, No. 9, e1006423, 01.09.2018.

Research output: Contribution to journalArticle

Migliore, R, Lupascu, CA, Bologna, LL, Romani, A, Courcol, JD, Antonel, S, Van Geit, WAH, Thomson, AM, Mercer, A, Lange, S, Falck, J, Rössert, CA, Shi, Y, Hagens, O, Pezzoli, M, Freund, T, Kali, S, Muller, EB, Schürmann, F, Markram, H & Migliore, M 2018, 'The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow', PLoS Computational Biology, vol. 14, no. 9, e1006423. https://doi.org/10.1371/journal.pcbi.1006423
Migliore, Rosanna ; Lupascu, Carmen A. ; Bologna, Luca L. ; Romani, Armando ; Courcol, Jean Denis ; Antonel, Stefano ; Van Geit, Werner A.H. ; Thomson, Alex M. ; Mercer, Audrey ; Lange, Sigrun ; Falck, Joanne ; Rössert, Christian A. ; Shi, Ying ; Hagens, Olivier ; Pezzoli, Maurizio ; Freund, T. ; Kali, Szabolcs ; Muller, Eilif B. ; Schürmann, Felix ; Markram, Henry ; Migliore, Michele. / The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow. In: PLoS Computational Biology. 2018 ; Vol. 14, No. 9.
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