Role of synaptic inhibition in turtle respiratory rhythm generation

In vitro brainstem and brainstem‐spinal cord preparations were used to determine the role of synaptic inhibition in respiratory rhythm generation in adult turtles. Bath application of bicuculline (a GABAA receptor antagonist) to brainstems increased hypoglossal burst frequency and amplitude, with peak discharge shifted towards the burst onset. Strychnine (a glycine receptor antagonist) increased amplitude and frequency, and decreased burst duration, but only at relatively high concentrations (10‐100 μM). Rhythmic activity persisted during combined bicuculline and strychnine application (50 μM each) with increased amplitude and frequency, decreased burst duration, and a rapid onset‐decrementing burst pattern. The bicuculline‐strychnine rhythm frequency decreased during μ‐opioid receptor activation or decreased bath PCO2. Synaptic inhibition blockade in the brainstem of brainstem‐spinal cord preparations increased burst amplitude in spinal expiratory (pectoralis) nerves and nearly abolished spinal inspiratory activity (serratus nerves), suggesting that medullary expiratory motoneurons were mainly active. Under conditions of synaptic inhibition blockade in vitro, the turtle respiratory network was able to produce a rhythm that was sensitive to characteristic respiratory stimuli, perhaps via an expiratory (rather than inspiratory) pacemaker‐driven mechanism. Thus, these data indicate that the adult turtle respiratory rhythm generator has the potential to operate in a pacemaker‐driven manner.

[1]  R. Russo,et al.  Inhibitory control of plateau properties in dorsal horn neurones in the turtle spinal cord in vitro , 1998, The Journal of physiology.

[2]  J. Feldman,et al.  Generation of respiratory rhythm and pattern in mammals: insights from developmental studies , 1995, Current Opinion in Neurobiology.

[3]  G. Mitchell,et al.  N-methyl-D-aspartate-mediated bulbospinal respiratory drive is pH/P(CO2)-insensitive in turtle brainstem-spinal cord. , 1998, Respiration physiology.

[4]  W M St John,et al.  Models of neuronal bursting behavior: implications for in-vivo versus in-vitro respiratory rhythmogenesis. , 2001, Advances in experimental medicine and biology.

[5]  Jan-Marino Ramirez,et al.  Role of Inspiratory Pacemaker Neurons in Mediating the Hypoxic Response of the Respiratory Network In Vitro , 2000, The Journal of Neuroscience.

[6]  Diethelm W. Richter,et al.  Mechanisms of respiratory rhythm generation , 1992, Current Opinion in Neurobiology.

[7]  Jc. Smith,et al.  Central respiratory pattern generation studied in an in vitro mammalian brainstem-spinal cord preparation , 1987 .

[8]  G. Mitchell,et al.  Episodic respiratory related discharge in turtle cranial motoneurons: in vivo and in vitro studies , 1990, Brain Research.

[9]  J. Remmers,et al.  Sites of respiratory rhythmogenesis during development in the tadpole. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[10]  D. Jackson,et al.  Ventilatory and Acid-Base Responses to Long-Term Hypercapnia in the Freshwater Turtle, Chrysemys Picta Bellii , 1985 .

[11]  C. Gans,et al.  The mechanism of lung ventilation in the tortoise Testudo graeca Linné. , 1967, The Journal of experimental biology.

[12]  P. Witkovsky,et al.  Calcium released from intracellular stores inhibits GABAA-mediated currents in ganglion cells of the turtle retina. , 1998, Journal of neurophysiology.

[13]  J. Ramirez,et al.  Mechanisms of respiratory rhythm generation change profoundly during early life in mice and rats , 1994, Neuroscience Letters.

[14]  Jan-Marino Ramirez,et al.  The neuronal mechanisms of respiratory rhythm generation , 1996, Current Opinion in Neurobiology.

[15]  J. Feldman,et al.  PreBötzinger complex and pacemaker neurons: hypothesized site and kernel for respiratory rhythm generation. , 1998, Annual review of physiology.

[16]  R. J. Wilson,et al.  Evidence that ventilatory rhythmogenesis in the frog involves two distinct neuronal oscillators , 2002, The Journal of physiology.

[17]  J. C. Smith,et al.  Cellular Mechanisms Underlying Modulation of Breathing Pattern in Mammals a , 1989, Annals of the New York Academy of Sciences.

[18]  K. M. Spyer,et al.  Studying rhythmogenesis of breathing: comparison of in vivo and in vitro models , 2001, Trends in Neurosciences.

[19]  N. Slater,et al.  GABAergic inhibition and epileptiform discharges in the turtle hippocampus in vitro , 1988, Brain Research.

[20]  A. Pack,et al.  Role of chloride‐mediated inhibition in respiratory rhythmogenesis in an in vitro brainstem of tadpole, Rana catesbeiana. , 1996, The Journal of physiology.

[21]  J. Ramirez,et al.  Unraveling the mechanism for respiratory rhythm generation. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[22]  J. Ramirez,et al.  Postnatal changes in the mammalian respiratory network as revealed by the transverse brainstem slice of mice. , 1996, The Journal of physiology.

[23]  S. Currie,et al.  Glycinergic Inhibition Contributes to the Generation of Rostral Scratch Motor Patterns in the Turtle Spinal Cord , 1997, The Journal of Neuroscience.

[24]  J. C. Smith,et al.  Pre-Bötzinger complex: a brainstem region that may generate respiratory rhythm in mammals. , 1991, Science.

[25]  R. A. Johnson,et al.  Hypoxia, temperature, and pH/CO2 effects on respiratory discharge from a turtle brain stem preparation. , 1998, Journal of applied physiology.

[26]  N. Mellen,et al.  Normal breathing requires preBötzinger complex neurokinin-1 receptor-expressing neurons , 2001, Nature Neuroscience.

[27]  K. Schmid,et al.  Glycine receptor-mediated fast synaptic inhibition in the brainstem respiratory system. , 1991, Respiration physiology.

[28]  J Duffin,et al.  Breathing Rhythm Generation: Focus on the Rostral Ventrolateral Medulla , 1995 .

[29]  J. Ramirez,et al.  Reconfiguration of the neural network controlling multiple breathing patterns: eupnea, sighs and gasps , 2000, Nature Neuroscience.

[30]  J. Ramirez,et al.  Selective lesioning of the cat pre‐Bötzinger complex in vivo eliminates breathing but not gasping , 1998, The Journal of physiology.

[31]  P. Ulinski,et al.  Role of GABAA-mediated inhibition in controlling the responses of regular spiking cells in turtle visual cortex , 2001, Visual Neuroscience.

[32]  J. Remmers,et al.  Postsynaptic potentials of bulbar respiratory neurons of the turtle. , 1986, Respiration physiology.

[33]  J. Ramirez,et al.  Respiratory rhythm generation in mammals: synaptic and membrane properties. , 1997, Respiration physiology.

[34]  J C Smith,et al.  Respiratory rhythm generation in neonatal and adult mammals: the hybrid pacemaker-network model. , 2000, Respiration physiology.

[35]  J. Champagnat,et al.  Electroresponsive properties and membrane potential trajectories of three types of inspiratory neurons in the newborn mouse brain stem in vitro. , 1996, Journal of neurophysiology.

[36]  Consuelo Morgado-Valle,et al.  Respiratory Rhythm An Emergent Network Property? , 2002, Neuron.

[37]  D. Richter,et al.  Blockade of synaptic inhibition within the pre‐Bötzinger complex in the cat suppresses respiratory rhythm generation in vivo , 1998, The Journal of physiology.

[38]  J. Feldman,et al.  Respiratory rhythm generation and synaptic inhibition of expiratory neurons in pre-Bötzinger complex: differential roles of glycinergic and GABAergic neural transmission. , 1997, Journal of neurophysiology.

[39]  J. C. Smith,et al.  Models of respiratory rhythm generation in the pre-Bötzinger complex. I. Bursting pacemaker neurons. , 1999, Journal of neurophysiology.

[40]  I. Rybak,et al.  Modeling neural mechanisms for genesis of respiratory rhythm and pattern. II. Network models of the central respiratory pattern generator. , 1997, Journal of neurophysiology.

[41]  J. Duffin,et al.  Respiratory rhythm generation , 1985, Canadian Anaesthetists' Society journal.

[42]  J. Paton,et al.  Reorganisation of respiratory network activity after loss of glycinergic inhibition , 2000, Pflügers Archiv.

[43]  P. Jonas,et al.  Corelease of two fast neurotransmitters at a central synapse. , 1998, Science.

[44]  J. C. Smith,et al.  Models of respiratory rhythm generation in the pre-Bötzinger complex. II. Populations Of coupled pacemaker neurons. , 1999, Journal of neurophysiology.

[45]  J. Ramirez,et al.  Identification of two types of inspiratory pacemaker neurons in the isolated respiratory neural network of mice. , 2001, Journal of neurophysiology.

[46]  D. Jones,et al.  The role of vagal afferent information and hypercapnia in control of the breathing pattern in chelonia. , 1980, The Journal of experimental biology.

[47]  C. Gans,et al.  Mechanics of respiration in the snapping turtle, Chelydra serpentina (Linné) , 1969 .

[48]  F. Mccutcheon.  The Respiratory Mechanism in Turtles , 1943, Physiological Zoology.

[49]  J. Remmers,et al.  The fictively breathing tadpole brainstem preparation as a model for the development of respiratory pattern generation and central chemoreception. , 1999, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[50]  Jeffrey C. Smith,et al.  Neuronal pacemaker for breathing visualized in vitro , 1999, Nature.

[51]  D. Richter,et al.  Role of fast inhibitory synaptic mechanisms in respiratory rhythm generation in the maturing mouse. , 1995, The Journal of physiology.

[52]  J C Smith,et al.  Pacemaker behavior of respiratory neurons in medullary slices from neonatal rat. , 1994, Journal of neurophysiology.

[53]  J. Lipski,et al.  The role of inhibitory amino acids in control of respiratory motor output in an arterially perfused rat. , 1992, Respiration physiology.

[54]  K. Ballanyi,et al.  Synaptic inhibition in the isolated respiratory network of neonatal rats , 1998, The European journal of neuroscience.

[55]  S. Perry,et al.  Strychnine eliminates reciprocation and augmentation of respiratory bursts of the in vitro frog brainstem , 1997, Neuroscience Letters.

[56]  A. J. Berger,et al.  Gap junctions and inhibitory synapses modulate inspiratory motoneuron synchronization. , 2001, Journal of neurophysiology.

[57]  J. C. Smith,et al.  Neurogenesis of respiratory rhythm and pattern: emerging concepts. , 1990, The American journal of physiology.

[58]  J C Smith,et al.  Isolation of the kernel for respiratory rhythm generation in a novel preparation: the pre-Bötzinger complex "island". , 2001, Journal of neurophysiology.