A stepwise neuron model fitting procedure designed for recordings with high spatial resolution: Application to layer 5 pyramidal cells

J Neurosci Methods. 2018 Jan 1;293:264-283. doi: 10.1016/j.jneumeth.2017.10.007. Epub 2017 Oct 7.


Background: Recent progress in electrophysiological and optical methods for neuronal recordings provides vast amounts of high-resolution data. In parallel, the development of computer technology has allowed simulation of ever-larger neuronal circuits. A challenge in taking advantage of these developments is the construction of single-cell and network models in a way that faithfully reproduces neuronal biophysics with subcellular level of details while keeping the simulation costs at an acceptable level.

New method: In this work, we develop and apply an automated, stepwise method for fitting a neuron model to data with fine spatial resolution, such as that achievable with voltage sensitive dyes (VSDs) and Ca2+ imaging.

Result: We apply our method to simulated data from layer 5 pyramidal cells (L5PCs) and construct a model with reduced neuronal morphology. We connect the reduced-morphology neurons into a network and validate against simulated data from a high-resolution L5PC network model.

Comparison with existing methods: Our approach combines features from several previously applied model-fitting strategies. The reduced-morphology neuron model obtained using our approach reliably reproduces the membrane-potential dynamics across the dendrites as predicted by the full-morphology model.

Conclusions: The network models produced using our method are cost-efficient and predict that interconnected L5PCs are able to amplify delta-range oscillatory inputs across a large range of network sizes and topologies, largely due to the medium after hyperpolarization mediated by the Ca2+-activated SK current.

Keywords: Automated fitting methods; Biophysically detailed modeling; Model fitting using imaging data; Multi-compartmental neuron models; Parameter peeling.

Publication types

  • Validation Study

MeSH terms

  • Animals
  • Automation, Laboratory / methods
  • Calcium / metabolism
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / physiology*
  • Computer Simulation
  • Dendrites / physiology
  • Image Processing, Computer-Assisted / methods
  • Ion Channels / metabolism
  • Membrane Potentials / physiology
  • Models, Neurological*
  • Pattern Recognition, Automated
  • Potassium / metabolism
  • Pyramidal Cells / cytology*
  • Pyramidal Cells / physiology*
  • Synapses / physiology
  • Voltage-Sensitive Dye Imaging / methods*


  • Ion Channels
  • Potassium
  • Calcium