A mathematical model of adult GnRH neurons in mouse brain and its bifurcation analysis

J Theor Biol. 2011 May 7;276(1):22-34. doi: 10.1016/j.jtbi.2011.01.035. Epub 2011 Feb 25.

Abstract

GnRH neurons are hypothalamic neurons that secrete gonadotropin-releasing hormone (GnRH) which stimulates the release of gonadotropins, one of the crucial hormones for sexual development, fertility and maturation. A mathematical model was built to help elucidate the mechanisms underlying electrical bursting and synchronous [Ca²(+)] transients in GnRH neurons (Lee et al., 2010). The model predicted that bursting in GnRH neurons (at least of the short-bursting type) requires the existence of a [Ca²(+)]-dependent slow after-hyperpolarisation current (sI(AHP-UCL)), and this predicted current was found experimentally. GnRH behaviour under a wide range of conditions (inhibition of Na(+) channels, IP₃ receptors, [Ca²(+)]-dependent K(+) channels, or Ca²(+) pumps, or in the presence of zero extracellular [Ca²(+)]) is successfully reproduced by the model. In this paper, a simplified version of the previous model, with the same qualitative behaviour, is constructed and studied using timescale separation techniques and bifurcation analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Aging / drug effects
  • Aging / physiology*
  • Animals
  • Apamin / pharmacology
  • Benzylamines / pharmacology
  • Boron Compounds / pharmacology
  • Brain / cytology*
  • Calcium / pharmacology
  • Computer Simulation
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Gonadotropin-Releasing Hormone / metabolism*
  • Indoles / pharmacology
  • Mice
  • Models, Biological*
  • Neurons / drug effects
  • Neurons / physiology*
  • Pyridines / pharmacology
  • Tetrodotoxin / pharmacology

Substances

  • 3-(triphenylmethylaminomethyl)pyridine
  • Benzylamines
  • Boron Compounds
  • Indoles
  • Pyridines
  • Apamin
  • Gonadotropin-Releasing Hormone
  • Tetrodotoxin
  • 2-aminoethoxydiphenyl borate
  • Calcium
  • cyclopiazonic acid