Efficient fitting of conductance-based model neurons from somatic current clamp

Nathan F. Lepora*, Paul G. Overton, Kevin Gurney

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

9 Citations (Scopus)

Abstract

Estimating biologically realistic model neurons from electrophysiological data is a key issue in neuroscience that is central to understanding neuronal function and network behavior. However, directly fitting detailed Hodgkin-Huxley type model neurons to somatic membrane potential data is a notoriously difficult optimization problem that can require hours/days of supercomputing time. Here we extend an efficient technique that indirectly matches neuronal currents derived from somatic membrane potential data to two-compartment model neurons with passive dendrites. In consequence, this approach can fit semi-realistic detailed model neurons in a few minutes. For validation, fits are obtained to model-derived data for various thalamo-cortical neuron types, including fast/regular spiking and bursting neurons. A key aspect of the validation is sensitivity testing to perturbations arising in experimental data, including sampling rates, inadequately estimated membrane dynamics/channel kinetics and intrinsic noise. We find that maximal conductance estimates and the resulting membrane potential fits diverge smoothly and monotonically from near-perfect matches when unperturbed. Curiously, some perturbations have little effect on the error because they are compensated by the fitted maximal conductances. Therefore, the extended current-based technique applies well under moderately inaccurate model assumptions, as required for application to experimental data. Furthermore, the accompanying perturbation analysis gives insights into neuronal homeostasis, whereby tuning intrinsic neuronal properties can compensate changes from development or neurodegeneration.

Original languageEnglish
Pages (from-to)1-24
Number of pages24
JournalJournal of Computational Neuroscience
Volume32
Issue number1
DOIs
Publication statusPublished - Feb 2012

Keywords

  • Conductance-based model neuron
  • Fast spiking neuron
  • Genesis
  • Hodgkin-Huxley model
  • Minimal model
  • Model fitting
  • Neocortex
  • Neuronal homeostasis
  • Optimization
  • Pyramidal neuron
  • Sensitivity

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