Journal Article

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

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

2018

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Action Potentials - physiology / Animals / Biology and Life Sciences / Biophysics / Brain research / Cell culture / Circuits / College campuses / Computer simulation / Conductance / Councils / Electrical properties / Electrophysiology / Firing pattern / Funding / Hippocampus / Hippocampus (Brain) / Hippocampus - physiology / Information technology / Interneurons / Interneurons - physiology / Ion channels / Kinases / Laboratories / Male / Mathematical models / Medicine and Health Sciences / Modelling / Models, Neurological / Neural circuitry / Neurons / Neurons - physiology / Physical Sciences / Physiological aspects / Physiology / Pyramidal cells / Pyramidal Cells - physiology / Rats / Rats, Sprague-Dawley / Resistance / Spatial distribution / Synaptic Transmission - physiology / University colleges / Variability / Workflow