Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons

PLoS Comput Biol. 2016 Feb 23;12(2):e1004761. doi: 10.1371/journal.pcbi.1004761. eCollection 2016 Feb.


The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics. For that, a new Generalized Integrate-and-Fire model featuring nonlinear firing threshold dynamics and conductance-based adaptation is introduced that outperforms state-of-the-art neuron models in predicting the spiking activity of neurons responding to a variety of in vivo-like fluctuating currents. Our model allows for efficient parameter extraction and can be analytically mapped to a Generalized Linear Model in which both the input filter--describing somatic integration--and the spike-history filter--accounting for spike-frequency adaptation--dynamically adapt to the input statistics, as experimentally observed. Overall, our results provide new insights on the computational role of different biophysical processes known to underlie adaptive coding in single neurons and support previous theoretical findings indicating that the nonlinear dynamics of the firing threshold due to Na+-channel inactivation regulate the sensitivity to rapid input fluctuations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Computational Biology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Neurological*
  • Neocortex / cytology*
  • Neocortex / physiology
  • Nonlinear Dynamics
  • Pyramidal Cells / physiology*

Grants and funding

This work was funded by: Swiss National Science Foundation (SNSF, grant numbers 200020_132871/1 and 200020_147200; http://www.snf.ch/fr/Pages/default.aspx) to CP SM; European Community’s Seventh Framework Program (BrainScaleS, grant no. 269921; http://cordis.europa.eu/fp7/home_en.html) to SM; European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 604102 (Human Brain Project; https://www.humanbrainproject.eu/) to CP; and a grant from the EPFL to the LNMC (http://markram-lab.epfl.ch/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.