ABSTRACT
We present in this paper a global methodology for the spike detection in a biological context of fluorescence recording of GnRH-neurons calcium activity. For this purpose we first propose a simple stochastic model that could mimic experimental time series by considering an autoregressive AR(1) process with a linear trend and specific innovations involving spiking times. Estimators of parameters with asymptotic normality are established and used to set up a statistical test on estimated innovations in order to detect spikes. We compare several procedures and illustrate on biological data the performance of our procedure.
Subject(s)
Calcium , Neurons , Action Potentials/physiology , Neurons/physiologyABSTRACT
Episodic release of GnRH is essential for reproductive function. In vitro studies have established that this episodic release is an endogenous property of GnRH neurons and that GnRH secretory pulses are associated with synchronization of GnRH neuron activity. The cellular mechanisms by which GnRH neurons synchronize remain largely unknown. There is no clear evidence of physical coupling of GnRH neurons through gap junctions to explain episodic synchronization. However, coupling of glial cells through gap junctions has been shown to regulate neuron activity in their microenvironment. The present study investigated whether glial cell communication through gap junctions plays a role in GnRH neuron activity and secretion in the mouse. Our findings show that Glial Fibrillary Acidic Protein-expressing glial cells located in the median eminence in close vicinity to GnRH fibers expressed Gja1 encoding connexin-43. To study the impact of glial-gap junction coupling on GnRH neuron activity, an in vitro model of primary cultures from mouse embryo nasal placodes was used. In this model, GnRH neurons possess a glial microenvironment and were able to release GnRH in an episodic manner. Our findings show that in vitro glial cells forming the microenvironment of GnRH neurons expressed connexin-43 and displayed functional gap junctions. Pharmacological blockade of the gap junctions with 50 µM 18-α-glycyrrhetinic acid decreased GnRH secretion by reducing pulse frequency and amplitude, suppressed neuronal synchronization and drastically reduced spontaneous electrical activity, all these effects were reversed upon 18-α-glycyrrhetinic acid washout.
Subject(s)
Gap Junctions/metabolism , Gonadotropin-Releasing Hormone/metabolism , Nerve Tissue Proteins/metabolism , Neuroglia/metabolism , Olfactory Mucosa/metabolism , Sensory Receptor Cells/metabolism , Animals , Biomarkers/metabolism , Cells, Cultured , Connexin 43/genetics , Connexin 43/metabolism , Embryo, Mammalian/cytology , Enzyme Inhibitors/pharmacology , Gap Junctions/drug effects , Gap Junctions/ultrastructure , Gene Expression Regulation, Developmental/drug effects , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Gonadotropin-Releasing Hormone/genetics , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Humans , Kinetics , Median Eminence/cytology , Median Eminence/drug effects , Median Eminence/metabolism , Mice, Transgenic , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/genetics , Neuroglia/drug effects , Neuroglia/ultrastructure , Neurotoxins/pharmacology , Olfactory Mucosa/drug effects , Olfactory Mucosa/ultrastructure , Recombinant Fusion Proteins/metabolism , Sensory Receptor Cells/drug effects , Sensory Receptor Cells/ultrastructure , Tissue Culture TechniquesABSTRACT
We describe a mathematical model of digestion in the small intestine. The main interest of our work is to consider simultaneously the different aspects of digestion i.e. transport of the bolus all along the intestine, feedstuffs degradation according to the enzymes and local physical conditions, and nutrients absorption. A system of coupled ordinary differential equations is used to model these phenomena. The major unknowns of this system are the position of the bolus and its composition. This system of equations is solved numerically. We present several numerical computations for the degradation, absorption and transport of the bolus with acceptable accuracy regarding the overall behavior of the model and also when challenged versus experimental data. The main feature and interest of this model are its genericity. Even if we are at an early stage of development, our approach can be adapted to deal with contrasted feedstuffs in non-ruminant animal to predict the composition and velocity of bolus in the small intestine.