Ionic current model of a hypoglossal motoneuron

We have developed a Hodgkin-Huxley type neuron model of a respiratory hypoglossal motoneuron (HM). The model consists of a single compartment containing a repertoire of ionic currents. The model reproduces several characteristics of HMs and accurately replicates the neuron's response to various pharmacological experiments. We also have studied the model's response to synaptic input, and its ability to integrate and transmit the inspiratory rhythm produced by the transverse slice preparation. The model provides explanations to how the cell produces the afterdepolarization and afterhyperpolarization seen in the HM action potential.

[1]  M. Umemiya,et al.  Single-channel properties of four calcium channel types in rat motoneurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  R. Lape,et al.  Characteristics of fast Na+ current of hypoglossal motoneurons in a rat brainstem slice preparation , 2001, The European journal of neuroscience.

[3]  S Cullheim,et al.  Three-dimensional architecture of dendritic trees in type-identified alpha-motoneurons. , 1987, The Journal of comparative neurology.

[4]  Bard Ermentrout,et al.  Simulating, analyzing, and animating dynamical systems - a guide to XPPAUT for researchers and students , 2002, Software, environments, tools.

[5]  M. Binder,et al.  Multiple mechanisms of spike-frequency adaptation in motoneurones , 1999, Journal of Physiology-Paris.

[6]  D. Bayliss,et al.  Calcium conductances and their role in the firing behavior of neonatal rat hypoglossal motoneurons. , 1993, Journal of neurophysiology.

[7]  D Schild,et al.  Small conductance potassium channels cause an activity-dependent spike frequency adaptation and make the transfer function of neurons logarithmic. , 1999, Biophysical journal.

[8]  W. Cameron,et al.  Anatomical and electrotonic coupling in developing genioglossal motoneurons of the rat , 1992, Brain Research.

[9]  R. Burke,et al.  Membrane area and dendritic structure in type‐identified triceps surae alpha motoneurons , 1987, The Journal of comparative neurology.

[10]  K. Magleby,et al.  Single apamin-blocked Ca-activated K+ channels of small conductance in cultured rat skeletal muscle , 1986, Nature.

[11]  M. Umemiya,et al.  Properties and function of low- and high-voltage-activated Ca2+ channels in hypoglossal motoneurons , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  Remmers Je,et al.  Pathogenesis of upper airway occlusion during sleep , 1978 .

[13]  J. Feldman,et al.  Synaptic control of motoneuronal excitability. , 2000, Physiological reviews.

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

[15]  J C Smith,et al.  Generation and transmission of respiratory oscillations in medullary slices: role of excitatory amino acids. , 1993, Journal of neurophysiology.

[16]  D A Bayliss,et al.  Multiple potassium conductances and their role in action potential repolarization and repetitive firing behavior of neonatal rat hypoglossal motoneurons. , 1993, Journal of neurophysiology.

[17]  O Hidaka,et al.  Role of calcium conductances on spike afterpotentials in rat trigeminal motoneurons. , 1997, Journal of neurophysiology.

[18]  S Fletcher,et al.  Somatic Colocalization of Rat SK1 and D class (Cav 1.2) L-type Calcium Channels in Rat CA1 Hippocampal Pyramidal Neurons , 2001, The Journal of Neuroscience.

[19]  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.

[20]  Donald R McCrimmon,et al.  Sodium currents in neurons from the rostroventrolateral medulla of the rat. , 2003, Journal of neurophysiology.

[21]  K. Mosier,et al.  Neural control of tongue movement with respect to respiration and swallowing. , 2001, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[22]  K. Spyer,et al.  Intracellular analysis of respiratory-modulated hypoglossal motoneurons in the cat , 1988, Neuroscience.

[23]  J. Mclarnon,et al.  Potassium currents in motoneurones , 1995, Progress in Neurobiology.

[24]  J C Smith,et al.  Models of respiratory rhythm generation in the pre-Bötzinger complex. III. Experimental tests of model predictions. , 2001, Journal of neurophysiology.

[25]  J. Leiter,et al.  Control and actions of the genioglossus muscle. , 1990, Progress in clinical and biological research.

[26]  F. Dudek,et al.  Riluzole-sensitive slowly inactivating sodium current in rat suprachiasmatic nucleus neurons. , 2004, Journal of neurophysiology.

[27]  R K Powers,et al.  Spike frequency adaptation studied in hypoglossal motoneurons of the rat. , 1995, Journal of neurophysiology.

[28]  W. Cameron,et al.  Morphology of developing rat genioglossal motoneurons studied in vitro: Relative changes in diameter and surface area of somata and dendrites , 1995, The Journal of comparative neurology.

[29]  D. Bayliss,et al.  Development of hypoglossal motoneurons. , 1996, Journal of applied physiology.

[30]  J. Feldman,et al.  Phrenic motoneuron morphology in the neonatal rat , 1991, The Journal of comparative neurology.

[31]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

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

[33]  R. Lape,et al.  Current and voltage clamp studies of the spike medium afterhyperpolarization of hypoglossal motoneurons in a rat brain stem slice preparation. , 2000, Journal of neurophysiology.

[34]  A. Lowe.  The neural regulation of tongue movements , 1980, Progress in Neurobiology.

[35]  Marc D Binder,et al.  Persistent sodium and calcium currents in rat hypoglossal motoneurons. , 2003, Journal of neurophysiology.

[36]  A. J. Berger.  Determinants of respiratory motoneuron output. , 2000, Respiration physiology.

[37]  W. Cameron,et al.  Time-dependent changes in input resistance of rat hypoglossal motoneurons associated with whole-cell recording. , 2000, Journal of neurophysiology.

[38]  W. Cameron,et al.  Physiological changes accompanying anatomical remodeling of mammalian motoneurons during postnatal development , 2000, Brain Research Bulletin.

[39]  G. Barrionuevo,et al.  Morphology of developing rat genioglossal motoneurons studied in vitro: Changes in length, branching pattern, and spatial distribution of dendrites , 1994, The Journal of comparative neurology.

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

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

[42]  P. A. Getting,et al.  Biophysical properties of hypoglossal neurons in vitro: intracellular studies in adult and neonatal rats. , 1990, Journal of applied physiology.

[43]  D A Bayliss,et al.  Repetitive firing properties of developing rat brainstem motoneurones. , 1995, The Journal of physiology.

[44]  M. Bellingham,et al.  Characteristics and postnatal development of a hyperpolarization-activated inward current in rat hypoglossal motoneurons in vitro. , 1994, Journal of neurophysiology.

[45]  D. Bayliss,et al.  Postnatal changes in rat hypoglossal motoneuron membrane properties , 1994, Neuroscience.

[46]  R. Miselis,et al.  Dendritic architecture of hypoglossal motoneurons projecting to extrinsic tongue musculature in the rat , 1994, The Journal of comparative neurology.

[47]  R K Powers,et al.  Contribution of outward currents to spike-frequency adaptation in hypoglossal motoneurons of the rat. , 1997, Journal of neurophysiology.

[48]  R K Powers,et al.  A variable-threshold motoneuron model that incorporates time- and voltage-dependent potassium and calcium conductances. , 1993, Journal of neurophysiology.

[49]  J. Rinzel,et al.  Compartmental model of vertebrate motoneurons for Ca2+-dependent spiking and plateau potentials under pharmacological treatment. , 1997, Journal of neurophysiology.

[50]  R. Lape,et al.  Voltage-activated K+ currents of hypoglossal motoneurons in a brain stem slice preparation from the neonatal rat. , 1999, Journal of neurophysiology.

[51]  N. Marrion,et al.  Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons , 1998, Nature.

[52]  A. Malhotra,et al.  Reduced genioglossal activity with upper airway anesthesia in awake patients with OSA. , 2000, Journal of applied physiology.

[53]  J. Remmers,et al.  Pathogenesis of upper airway occlusion during sleep. , 1978, Journal of applied physiology: respiratory, environmental and exercise physiology.

[54]  A. J. Berger,et al.  Double- and triple-labeling of functionally characterized central neurons projecting to peripheral targets studied in vitro , 1990, Neuroscience.

[55]  Richard Bertram,et al.  A computational study of the effects of serotonin on a molluscan burster neuron , 1993, Biological Cybernetics.

[56]  John Rinzel,et al.  A minimal, compartmental model for a dendritic origin of bistability of motoneuron firing patterns , 1995, Journal of Computational Neuroscience.

[57]  J. Rekling,et al.  Electrophysiological properties of hypoglossal motoneurons of guinea-pigs studied in vitro , 1989, Neuroscience.