Document Type
Article
Publication Title
PLoS ONE
Publisher
Public Library of Science
Publication Date
10-31-2014
Volume
9
Issue
10
Disciplines
Medical Sciences | Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
Abstract
Multi-compartmental models of neurons provide insight into the complex, integrative properties of dendrites. Because it is not feasible to experimentally determine the exact density and kinetics of each channel type in every neuronal compartment, an essential goal in developing models is to help characterize these properties. To address biological variability inherent in a given neuronal type, there has been a shift away from using hand-tuned models towards using ensembles or populations of models. In collectively capturing a neuron’s output, ensemble modeling approaches uncover important conductance balances that control neuronal dynamics. However, conductances are never entirely known for a given neuron class in terms of its types, densities, kinetics and distributions. Thus, any multi-compartment model will always be incomplete. In this work, our main goal is to use ensemble modeling as an investigative tool of a neuron’s biophysical balances, where the cycling between experiment and model is a design criterion from the start. We consider orienslacunosum/ moleculare (O-LM) interneurons, a prominent interneuron subtype that plays an essential gating role of information flow in hippocampus. O-LM cells express the hyperpolarization-activated current (Ih). Although dendritic Ih could have a major influence on the integrative properties of O-LM cells, the compartmental distribution of Ih on O-LM dendrites is not known. Using a high-performance computing cluster, we generated a database of models that included those with or without dendritic Ih. A range of conductance values for nine different conductance types were used, and different morphologies explored. Models were quantified and ranked based on minimal error compared to a dataset of OLM cell electrophysiological properties. Co-regulatory balances between conductances were revealed, two of which were dependent on the presence of dendritic Ih. These findings inform future experiments that differentiate between somatic and dendritic Ih, thereby continuing a cycle between model and experiment.
DOI
10.1371/journal.pone.0106567
Rights
© 2014 Sekulic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Recommended Citation
Sekulic´ V, Lawrence JJ, Skinner FK (2014) Using Multi-Compartment Ensemble Modeling As an Investigative Tool of Spatially Distributed Biophysical Balances: Application to Hippocampal Oriens-Lacunosum/Moleculare (O-LM) Cells. PLoS ONE 9(10): e106567. doi:10.1371/journal.pone.0106567