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      Electrophysiology of Hypothalamic Magnocellular Neurons In vitro: A Rhythmic Drive in Organotypic Cultures and Acute Slices

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          Abstract

          Hypothalamic neurohormones are released in a pulsatile manner. The mechanisms of this pulsatility remain poorly understood and several hypotheses are available, depending upon the neuroendocrine system considered. Among these systems, hypothalamo-neurohypophyseal magnocellular neurons have been early-considered models, as they typically display an electrical activity consisting of bursts of action potentials that is optimal for the release of boluses of the neurohormones oxytocin and vasopressin. The cellular mechanisms underlying this bursting behavior have been studied in vitro, using either acute slices of the adult hypothalamus, or organotypic cultures of neonatal hypothalamic tissue. We have recently proposed, from experiments in organotypic cultures, that specific central pattern generator networks, upstream of magnocellular neurons, determine their bursting activity. Here, we have tested whether a similar hypothesis can be derived from in vitro experiments in acute slices of the adult hypothalamus. To this aim we have screened our electrophysiological recordings of the magnocellular neurons, previously obtained from acute slices, with an analysis of autocorrelation of action potentials to detect a rhythmic drive as we recently did for organotypic cultures. This confirmed that the bursting behavior of magnocellular neurons is governed by central pattern generator networks whose rhythmic drive, and thus probably integrity, is however less satisfactorily preserved in the acute slices from adult brains.

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          Organization of mammalian locomotor rhythm and pattern generation.

          Central pattern generators (CPGs) located in the spinal cord produce the coordinated activation of flexor and extensor motoneurons during locomotion. Previously proposed architectures for the spinal locomotor CPG have included the classical half-center oscillator and the unit burst generator (UBG) comprised of multiple coupled oscillators. We have recently proposed another organization in which a two-level CPG has a common rhythm generator (RG) that controls the operation of the pattern formation (PF) circuitry responsible for motoneuron activation. These architectures are discussed in relation to recent data obtained during fictive locomotion in the decerebrate cat. The data show that the CPG can maintain the period and phase of locomotor oscillations both during spontaneous deletions of motoneuron activity and during sensory stimulation affecting motoneuron activity throughout the limb. The proposed two-level CPG organization has been investigated with a computational model which incorporates interactions between the CPG, spinal circuits and afferent inputs. The model includes interacting populations of spinal interneurons and motoneurons modeled in the Hodgkin-Huxley style. Our simulations demonstrate that a relatively simple CPG with separate RG and PF networks can realistically reproduce many experimental phenomena including spontaneous deletions of motoneuron activity and a variety of effects of afferent stimulation. The model suggests plausible explanations for a number of features of real CPG operation that would be difficult to explain in the framework of the classical single-level CPG organization. Some modeling predictions and directions for further studies of locomotor CPG organization are discussed.
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            The motor infrastructure: from ion channels to neuronal networks.

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              Neuropeptides: opportunities for drug discovery.

              The role of peptides as signalling molecules in the nervous system has been studied for more than 30 years. Neuropeptides and their G-protein-coupled receptors are widely distributed throughout the body and they commonly occur with, and are complementary to, classic neurotransmitters. The functions of neuropeptides range from neurotransmitter to growth factor. They are present in glial cells, are hormones in the endocrine system, and are messengers in the immune system. Much evidence indicates that neuropeptides are of particular importance when the nervous system is challenged (eg, by stress, injury, or drug abuse). These features and the large number of neuropeptides and neuropeptide receptors provide many opportunities for the discovery of new drug targets for the treatment of nervous-system disorders. In fact, receptor-subtype-selective antagonists and agonists have been developed, and recently a substance P receptor (neurokinin 1) antagonist has been shown to have clinical efficacy in the treatment of major depression and chemotherapy-induced emesis. Several other neuropeptide receptor ligands are in clinical trials for various indications.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                31 March 2016
                2016
                : 10
                : 109
                Affiliations
                [1] 1U1215, Neurocentre Magendie, Institut National de la Santé et de la Recherche Médicale Bordeaux, France
                [2] 2Université de Bordeaux Bordeaux, France
                Author notes

                Edited by: Sebastien G. Bouret, University of Southern California, USA

                Reviewed by: Oline K. Ronnekleiv, Oregon Health and Science University, USA; Vance Trudeau, University of Ottawa, Canada

                *Correspondence: Philippe Ciofi philippe.ciofi@ 123456inserm.fr

                This article was submitted to Neuroendocrine Science, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2016.00109
                4814512
                27065780
                c15b382e-8717-45b5-85d0-7df47365b142
                Copyright © 2016 Israel, Oliet and Ciofi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 January 2016
                : 07 March 2016
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 55, Pages: 13, Words: 8721
                Categories
                Endocrinology
                Hypothesis and Theory

                Neurosciences
                burst firing,oxytocin,pulse generator,supraoptic nucleus,vasopressin
                Neurosciences
                burst firing, oxytocin, pulse generator, supraoptic nucleus, vasopressin

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