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Modeling electrical spiking, bursting and calcium dynamics in gonadotropin releasing hormone (GnRH) secreting neurons

The plasma membrane electrical activities of neurons that secrete gonadotropin releasing
hormone (GnRH), referred to as GnRH neurons hereafter, have been studied extensively.
A couple of mathematical models have been developed previously to explain different
aspects of these activities including spontaneous spiking and responses to stimuli such as current injections, GnRH, thapsigargin (Tg) and apamin. The goal of this paper is to
develop one single, minimal model that accounts for the experimental results reproduced
by previously existing models and results that were not accounted for by these models.
The latter includes two types of membrane potential bursting mechanisms and the
associated calcium oscillations in the cytosol. One of them has not been reported in
experimental literatures on GnRH neurons and is thus regarded as a model prediction.
Other improvements achieved in this model include the incorporation of a more detailed
description of calcium dynamics in a three dimensional cell body with the ion channels
evenly distributed on the cell surface. Although the model is mainly based on data
collected in cultured GnRH cell lines, we show that it is capable of explaining some
properties of GnRH neurons observed in several of other preparations including mature
GnRH neurons in hypothalamic slices. One potential explanation is suggested. A
phenomenological reduction of this model into a simplified form is presented. The
simplified model will facilitate the study of the roles of plasma membrane electrical
activities on the pulsatile release of GnRH by these neurons when it is coupled with a
model of pulsatile GnRH release based on the autoregulation mechanism.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU.2429/2574
Date11 1900
CreatorsFletcher, Patrick Allen
PublisherUniversity of British Columbia
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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