NMDA Actions on Rat Abducens Motoneurons

Intracellular recordings were made from rat abducens motoneurons in vivo during local extracellular micro‐ionophoretic application of N‐methyl‐d‐aspartate (NMDA) and NMDA receptor antagonists. Typical NMDA responses, at a resting potential of –60 mV, consisted of a slow depolarization with an apparent increase in membrane resistance, bursts of action potentials followed by stable repetitive firing, lonophoretic applications of aminophosphonovalerate (APV), kynurenate or MK801 reduced or blocked the NMDA‐induced responses. The NMDA responses were voltage‐dependent. NMDA responses induced by short (< 30 s) NMDA application pulses were blocked by hyperpolarizing the neuron. Long duration (> 30 s) NMDA applications induced rhythmic plateau potentials in hyperpolarized abducens motoneurons. The rhythmic depolarizations (15–30 mV) were modulated in both frequency and duration by current injection. They were abolished by further hyperpolarization or replaced by stable repetitive firing when hyperpolarization was removed. Our data show that NMDA receptors are present in rat abducens motoneurons and may be involved in the induction of rhythmic activities. The voltage‐dependent blockade of somatic NMDA receptor‐associated ion channels by cell hyperpolarization may be important for these oscillations. It is suggested that the rhythmic behaviour is due to the activation of dendritic NMDA receptors.

[1]  J. Watkins,et al.  2-Amino-5-phosphonovalerate (2APV), a potent and selective antagonist of amino acid-induced and synaptic excitation , 1981, Neuroscience Letters.

[2]  B. Bean,et al.  Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Y Shinoda,et al.  Nature of synaptic events in cat abducens motoneurons at slow and quick phase of vestibular nystagmus. , 1972, Journal of neurophysiology.

[4]  K. Grant,et al.  The activity of identified secondary vestibular neurons during nystagmus , 1976, Brain Research.

[5]  L. Nowak,et al.  N‐methyl‐D‐aspartate‐activated channels of mouse central neurones in magnesium‐free solutions. , 1988, The Journal of physiology.

[6]  J. Buchanan.  Neural Control of Locomotion in Lower Vertebrates: From Behavior to Ionic Mechanisms , 1988 .

[7]  R. S. Jones.  The NMDA receptor Edited by J. C. Watkins and G. L. Collinridge. Oxford University Press, New York (1990) 242 pp. £45.00 , 1991, Neuroscience.

[8]  A. Thomson,et al.  Comparison of responses to transmitter candidates at an N-methylaspartate receptor mediated synapse, in slices of rat cerebral cortex , 1986, Neuroscience.

[9]  M. Cuénod,et al.  l-Homocysteic acid but not l-glutamate is an endogenous N-methyl-d-aspartic acid receptor preferring agonist in rat neocortical neurons in vitro , 1987, Neuroscience Letters.

[10]  K. Sigvardt,et al.  Excitatory neurotransmission activates voltage-dependent properties in neurons in spinal motor system of lamprey. , 1989, Journal of neurophysiology.

[11]  S. Grillner,et al.  The ionic mechanisms underlying N-methyl-d-aspartate receptor-induced, tetrodotoxin-resistant membrane potential oscillations in lamprey neurons active during locomotion , 1985, Neuroscience Letters.

[12]  J. A. Peters,et al.  The mechanism of action and pharmacological specificity of the anticonvulsant NMDA antagonist MK‐801: a voltage clamp study on neuronal cells in culture , 1989, British journal of pharmacology.

[13]  M. Luyckx,et al.  [Excitatory amino acid receptors]. , 1991, Journal de pharmacie de Belgique.

[14]  J. Durand,et al.  Excitatory amino acid actions on membrane potential and conductance of brainstem motoneurones , 1990 .

[15]  S. Massey,et al.  Glutamate receptors of ganglion cells in the rabbit retina: evidence for glutamate as a bipolar cell transmitter. , 1988, The Journal of physiology.

[16]  R. Dingledine.  N‐methyl aspartate activates voltage‐dependent calcium conductance in rat hippocampal pyramidal cells. , 1983, The Journal of physiology.

[17]  L. A. Segade,et al.  Localisation of motoneurons supplying the extra-ocular muscles of the rat using horseradish peroxidase and fluorescent double labelling. , 1983 .

[18]  J. Macdonald,et al.  Two conductance mechanisms activated by applications of L-glutamic, L-aspartic, DL-homocysteic, N-methyl-D-aspartic, and DL-kainic acids to cultured mammalian central neurones. , 1980, Canadian journal of physiology and pharmacology.

[19]  J. Macdonald,et al.  L-aspartic acid induces a region of negative slope conductance in the current-voltage relationship of cultured spinal cord neurons , 1982, Brain Research.

[20]  A. Selverston,et al.  The Crustacean Stomatogastric System , 1987, Springer Berlin Heidelberg.

[21]  M. Mayer,et al.  Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones , 1984, Nature.

[22]  T E Salt,et al.  Effects of excitatory amino acids and their antagonists on membrane and action potentials of cat caudate neurones. , 1983, The Journal of physiology.

[23]  S. Grillner,et al.  Transmitters, membrane properties and network circuitry in the control of locomotion in lamprey , 1987, Trends in Neurosciences.

[24]  I. Engberg,et al.  An Analysis Of Bioelectrical Phenomena Evoked By Microiontophoretically Applied Excitotoxic Amino-Acids In The Feline Spinal Cord , 1983 .

[25]  J. Hounsgaard,et al.  Calcium conductance and firing properties of spinal motoneurones in the turtle. , 1988, The Journal of physiology.

[26]  L. Nowak,et al.  Electrophysiological studies of NMDA receptors , 1987, Trends in Neurosciences.

[27]  J. Lambert,et al.  The interaction between barbiturate anaesthetics and excitatory amino acid responses on cat spinal neurones , 1981, Neuropharmacology.

[28]  S. Grillner,et al.  N-methyl-D-aspartate receptor-induced, inherent oscillatory activity in neurons active during fictive locomotion in the lamprey , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  O. Hikosaka,et al.  Postsynaptic inhibition underlying spike suppression of secondary vestibular neurons during quick phases of vestibular nystagmus , 1980, Neuroscience Letters.

[30]  M. Mayer,et al.  Sites of antagonist action on N-methyl-D-aspartic acid receptors studied using fluctuation analysis and a rapid perfusion technique. , 1988, Journal of neurophysiology.

[31]  P. C. Schwindt,et al.  The induction and modification of voltage-sensitive responses in cat neocortical nuerons by N-methyl-d-aspartate , 1986, Brain Research.

[32]  J. Hablitz,et al.  EPSPs in rat neocortical neurons in vitro. I. Electrophysiological evidence for two distinct EPSPs. , 1989, Journal of neurophysiology.

[33]  Y. Ben-Ari,et al.  Endogenous and network bursts induced by N-methyl-d-aspartate and magnesium free medium in the CA3 region of the hippocampal slice , 1989, Neuroscience.

[34]  I. Engberg,et al.  The actions of excitatory amino acids on motoneurones in the feline spinal cord. , 1979, The Journal of physiology.

[35]  L. Nowak,et al.  Magnesium gates glutamate-activated channels in mouse central neurones , 1984, Nature.

[36]  P. Schwindt,et al.  Multiple actions of N-methyl-d-aspartate on cat neocortical neurons in vitro , 1983, Brain Research.

[37]  L. Nowak,et al.  The role of divalent cations in the N‐methyl‐D‐aspartate responses of mouse central neurones in culture. , 1988, The Journal of physiology.

[38]  J. Hablitz,et al.  EPSPs in rat neocortical neurons in vitro. II. Involvement of N-methyl-D-aspartate receptors in the generation of EPSPs. , 1989, Journal of neurophysiology.

[39]  P. Stanzione,et al.  Excitatory amino acids in synaptic excitation of rat striatal neurones in vitro. , 1988, The Journal of physiology.

[40]  C. Cotman,et al.  The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. , 1989, Annual review of pharmacology and toxicology.

[41]  R. Llinás,et al.  Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. , 1980, The Journal of physiology.

[42]  H Wachtel,et al.  Negative Resistance Characteristic Essential for the Maintenance of Slow Oscillations in Bursting Neurons , 1974, Science.

[43]  L. Iversen,et al.  The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[44]  R K Wong,et al.  Sustained dendritic gradients of Ca2+ induced by excitatory amino acids in CA1 hippocampal neurons. , 1988, Science.

[45]  D. Lodge,et al.  Differences in results from in vivo and in vitro studies on the use-dependency of N-methylaspartate antagonism by MK-801 and other phencyclidine receptor ligands. , 1988, European journal of pharmacology.

[46]  I. Engberg,et al.  l-Glutamate and N-methyl-d-aspartate actions on membrane potential and conductance of cat abducens motoneurones , 1987, Neuroscience Letters.

[47]  I. Engberg,et al.  The variation in action of excitatory amino acids in relation to distance of iontophoretic application to spinal motoneurones. , 1985, Acta physiologica Scandinavica.

[48]  A. Ganong,et al.  Excitatory amino acid neurotransmission: NMDA receptors and Hebb-type synaptic plasticity. , 1988, Annual review of neuroscience.

[49]  A. M. Etgen,et al.  Estradiol regulates the number of α1 but not β or α2 noradrenergic receptors in hypothalamus of female rats , 1990, Neurochemistry International.

[50]  T. Sears,et al.  Effect of glutamate, aspartate and related derivatives on cerebellar Purkinje cell dendrites in the rat: an in vitro study , 1982, The Journal of physiology.

[51]  H. Gainer,et al.  Requirements for bursting pacemaker potential activity in molluscan neurones , 1975, Nature.

[52]  Stephen J. Smith,et al.  NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones , 1986, Nature.

[53]  Y. Ben-Ari.  Excitatory Amino Acids and Neuronal Plasticity , 1990, Advances in Experimental Medicine and Biology.

[54]  L. Iversen,et al.  Excitatory amino acids in the brain - focus on NMDA receptors , 1987, Trends in Neurosciences.

[55]  D. F. Russell,et al.  Bursting neural networks: a reexamination. , 1978, Science.

[56]  S. Grillner,et al.  Activation of NMDA receptors elecits fictive locomotion and bistable membrane properties in the lamprey spinal cord , 1985, Brain Research.

[57]  P. S. Dickinson,et al.  Control of a central pattern generator by an identified modulatory interneurone in crustacea. II. Induction and modification of plateau properties in pyloric neurones. , 1983, The Journal of experimental biology.

[58]  M. Mayer,et al.  The physiology of excitatory amino acids in the vertebrate central nervous system , 1987, Progress in Neurobiology.

[59]  V. Crunelli,et al.  The reversal potential of excitatory amino acid action on granule cells of the rat dentate gyrus. , 1984, The Journal of physiology.

[60]  B. Cabrera,et al.  Location of motoneurons and internuclear neurons within the rat abducens nucleus by means of horseradish peroxidase and fluorescent double labeling , 1988, Neuroscience Letters.