A homeostatic model of neuronal firing governed by feedback signals from the extracellular matrix

PLoS One. 2012;7(7):e41646. doi: 10.1371/journal.pone.0041646. Epub 2012 Jul 27.

Abstract

Molecules of the extracellular matrix (ECM) can modulate the efficacy of synaptic transmission and neuronal excitability. These mechanisms are crucial for the homeostatic regulation of neuronal firing over extended timescales. In this study, we introduce a simple mathematical model of neuronal spiking balanced by the influence of the ECM. We consider a neuron receiving random synaptic input in the form of Poisson spike trains and the ECM, which is modeled by a phenomenological variable involved in two feedback mechanisms. One feedback mechanism scales the values of the input synaptic conductance to compensate for changes in firing rate. The second feedback accounts for slow fluctuations of the excitation threshold and depends on the ECM concentration. We show that the ECM-mediated feedback acts as a robust mechanism to provide a homeostatic adjustment of the average firing rate. Interestingly, the activation of feedback mechanisms may lead to a bistability in which two different stable levels of average firing rates can coexist in a spiking network. We discuss the mechanisms of the bistability and how they may be related to memory function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Extracellular Matrix / metabolism*
  • Feedback, Physiological*
  • Homeostasis*
  • Models, Neurological*
  • Neurons / cytology*
  • Neurons / metabolism
  • Peptide Hydrolases / metabolism
  • Receptors, Neurotransmitter / metabolism
  • Signal Transduction*
  • Time Factors

Substances

  • Receptors, Neurotransmitter
  • Peptide Hydrolases