title: A unified model for two modes of bursting in GnRH neurons.
abstract: Gonadotropin-releasing hormone (GnRH) neurons exhibit at least two intrinsic modes of action potential burst firing, referred to as parabolic and irregular bursting. Parabolic bursting is characterized by a slow wave in membrane potential that can underlie periodic clusters of action potentials with increased interspike interval at the beginning and at the end of each cluster. Irregular bursting is characterized by clusters of action potentials that are separated by varying durations of interburst intervals and a relatively stable baseline potential. Based on recent studies of isolated ionic currents, a stochastic Hodgkin-Huxley (HH)-like model for the GnRH neuron is developed to reproduce each mode of burst firing with an appropriate set of conductances. Model outcomes for bursting are in agreement with the experimental recordings in terms of interburst interval, interspike interval, active phase duration, and other quantitative properties specific to each mode of bursting. The model also shows similar outcomes in membrane potential to those seen experimentally when tetrodotoxin (TTX) is used to block action potentials during bursting, and when estradiol transitions cells exhibiting slow oscillations to irregular bursting mode in vitro. Based on the parameter values used to reproduce each mode of bursting, the model suggests that GnRH neurons can switch between the two through changes in the maximum conductance of certain ionic currents, notably the slow inward Ca(2+) current I s, and the Ca(2+) -activated K(+) current I KCa. Bifurcation analysis of the model shows that both modes of bursting are similar from a dynamical systems perspective despite differences in burst characteristics.
authors.affiliation: Department of Physiology, McGill University, Montreal, QC, H3G 1Y6, Canada.
authors.forename: Spencer
authors.initials: S
authors.lastname: Moran
authors.affiliation: Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.|Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, 48109, USA.|Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Moenter
authors.affiliation: Department of Physiology, McGill University, Montreal, QC, H3G 1Y6, Canada. anmar.khadra@mcgill.ca.
authors.forename: Anmar
authors.initials: A
authors.lastname: Khadra
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D007987:Gonadotropin-Releasing Hormone; D013779:Tetrodotoxin
keywords: Estradiol feedback; Irregular bursting; Mathematical model; Parabolic bursting; Slow oscillations; Slow-fast subsystem analysis