Low-dimensional, morphologically accurate models of subthreshold membrane potential

J Comput Neurosci. 2009 Oct;27(2):161-76. doi: 10.1007/s10827-008-0134-2. Epub 2009 Jan 27.

Abstract

The accurate simulation of a neuron's ability to integrate distributed synaptic input typically requires the simultaneous solution of tens of thousands of ordinary differential equations. For, in order to understand how a cell distinguishes between input patterns we apparently need a model that is biophysically accurate down to the space scale of a single spine, i.e., 1 mum. We argue here that one can retain this highly detailed input structure while dramatically reducing the overall system dimension if one is content to accurately reproduce the associated membrane potential at a small number of places, e.g., at the site of action potential initiation, under subthreshold stimulation. The latter hypothesis permits us to approximate the active cell model with an associated quasi-active model, which in turn we reduce by both time-domain (Balanced Truncation) and frequency-domain (H(2) approximation of the transfer function) methods. We apply and contrast these methods on a suite of typical cells, achieving up to four orders of magnitude in dimension reduction and an associated speed-up in the simulation of dendritic democratization and resonance. We also append a threshold mechanism and indicate that this reduction has the potential to deliver an accurate quasi-integrate and fire model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Algorithms
  • Animals
  • Axons / physiology
  • Cell Membrane / physiology*
  • Central Nervous System / physiology*
  • Computer Simulation*
  • Dendrites / physiology
  • Humans
  • Ion Channels / physiology
  • Kinetics
  • Linear Models
  • Membrane Potentials / physiology*
  • Neural Pathways / physiology
  • Neurons / physiology*
  • Rats
  • Synaptic Transmission / physiology*

Substances

  • Ion Channels