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Excitatory amino acid receptors in normal and abnormal vestibular function

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Although excitatory amino acid (FAA) receptors have been investigated extensively in the limbic system and neocortex, less is known of the function of EAA receptors in the brainstem. A number of biochemical and electrophysiological studies suggest that the synapse between the ipsilateral vestibular (VIIIth) nerve and the brainstem vestibular nucleus (VN) is mediated by an EAA acting predominantly on kainate or α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. In addition, there is electrophysiological evidence that input from the contralateral vestibular nerve via the contralateral VN is partially mediated byN-methyl-d-aspartate (NMDA) receptors. Input to the VN from the spinal cord may also be partially mediated by NMDA receptors. All of the electrophysiological studies conducted so far have used in vitro preparations, and it is possible that denervation of the VN during the preparation of an explant or slice causes changes in EAA receptor function. Nonetheless, these results suggest that EAA receptors may be important in many different parts of the vestibular reflex pathways. Studies of the peripheral vestibular system have also shown that EAAs are involved in transmission between the receptor hair cells and the vestibular nerve fibers. A number of recent studies in the area of vestibular plasticity have reported that antagonists for the NMDA receptor subtype disrupt the behavioral recovery that occurs following unilateral deafferentation of the vestibular nerve fibers (vestibular compensation). It has been suggested that vestibular compensation may be owing to an upregulation or increased affinity of NMDA receptors in the VN ipsilateral to the peripheral deafferentation; however; at present, there is no clear evidence to support this hypothesis.

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  1. Alford S. and Williams T. L. (1989) Endogenous activation of glycine and NMDA receptors in lamprey spinal cord during fictive locomotion.J. Neurosci. 9, 2792–2800.

  2. Annoni J. M., Cochran S. L., and Precht W. (1984) Pharmacology of the vestibular hair cells afferent fiber synapse in the frog.J. Neurosci. 4, 2106–2116.

  3. Billard J. M. and Fumain R. (1989) Loss ofN-methyl-d-aspartate sensitivity of cerebellar Purkinje cells after climbing fiber deafferentation. An in vivo study in the rat.Neurosci. Lett. 106, 199–204.

  4. Burgoyne R. D., Pearce I. A., and Cambray-Deakin M. (1988)N-methyl-d-aspartate raises cytosolic calcium concentration in rat cerebellar granule cells in culture.Neurosci. Lett. 91, 47–52.

  5. Cass S. P. and Goshgarian H. G. (1991) Vestibular compensation after labyrinthectomy and vestibular neurectomy in cats.Otolaryngol. Head Neck Surg. 104, 14–19.

  6. Cazalets J. R., Grillner P., Menard I., Cremieux J., and Clarac F. (1990) Two types of motor rhythm induced by NMDA and amines in an in vitro spinal cord preparation of neonatal rat.Neurosci. Lett. 111, 116–121.

  7. Cochran S., Kasik P., and Precht W. (1987) Pharmacological aspects of excitatory synaptic transmission to second-order vestibular neurons in the frog.Synapse.1, 102–123.

  8. Collingridge G. L. and Bliss T. V. P. (1987) NMDA receptors—their role in long term potentiation.Trends Neurosci. 10, 288–293.

  9. Collingridge G. L. and Lester R. A. J. (1989) Excitatory amino acid receptors in the vertebrate central nervous system.Pharmacol. Revs. 40, 143–210.

  10. Darlington C. L. and Smith P. F. (1989) The effects ofN-methyl-d-aspartate antagonists on the development of vestibular compensation in the guinea pig.Eur. J. Pharmacol. 174, 273–278.

  11. Davies S. N., Martin D., Millar J. D., Aram J. A., Church J., and Lodge D. (1988) Differences in results from in vivo and in vitro studies on the use-dependency ofN-methylaspartate antagonism by MK801 and other phencyclidine receptor ligands.Eur. J. Pharmacol. 145, 141–151.

  12. Dechesne C., Raymond J., and Dans A. (1984) The action of glutamate in the cat labyrinth.Ann. Otol. Rhinol. Laryngol. 93, 163–165.

  13. Dechesne C. J., Hampson D. R., Goping G., Wheaton K. D., and Wenthold R. J. (1991) Identification and localization of a kainate binding protein in the frog inner ear by electron microscopy immunocytochemistry.Brain Res. 545, 223–233.

  14. Dememes D., Raymond J., and Sans A. (1984) Selective retrograde labelling of neurons of the cat vestibular ganglion with [3H]d-Aspartate.Brain Res. 304, 188–191.

  15. de Waele C., Serafin M., Muhlethaler M., and Vidal P. P. (1989) Neurochemical aspects of vestibular compensation.Vestibular Compensation: Facts, Theories and Clinical Perspectives. Lacour M., Toupet M., Denise P., and Christen Y, eds., Elsevier, Paris, pp. 95–104.

  16. de Waele C., Vibert N., Baudrimont M., and Vidal P. P. (1990) NMDA receptors contribute to the resting discharge of vestibular neurons in the normal and hemilabyrinthetomized guinea pig.Exp. Brain Res. 81, 125–133.

  17. Dieringer N. and Precht W. (1977) Modification of synaptic input following unilateral labyrinthectomy.Nature. 269, 431–433.

  18. Doi K., Tsumoto T., and Matsunaga T. (1990) Actions of excitatory amino acid antagonists on synaptic inputs to the rat medial vestibular nucleus: an electrophysiological study in vitro.Exp. Brain Res. 82, 254–262.

  19. Durand J., Engberg I., and Tyc-Dumont S. (1987) Glutamate andN-methyl-d-aspartate actions on membrane potential and conductance of cat abducens motoneurones.Neurosci. Lett. 79, 295–300.

  20. Dye J., Heiligenberg W., Keller C. H., and Kawasaki M. (1989) Different classes of glutamate receptors mediate distinct behaviors in a single brainstem nucleus.Proc. Natl. Acad. Sci. USA 86, 8993–8997.

  21. Flohr H., Burt A., Will U., and Ammelburg R. (1989) Vestibular compensation: a paradigm for lesioninduced neural plasticity.Fundementals of Memory Formation: Neuronal Plasticity and Brain Function. Rahmann, R., ed., Springer, Struttgrat, pp. 243–260.

  22. Forsythe I. D. and Westbrook G. L. (1988) Slow excitatory postsynaptic currents mediated byN-methyl-d-aspartate receptors on cultured mouse central neurones.J. Physiol. 396, 515–533.

  23. Gallagher J. P., Lewis M. R., and Shinnick-Gallagher P. (1985) An electrophysiological investigation of the rat medial vestibular nucleus in vitro.Contemporary Sensory Neurobiology. Correia M. J. and Perachio A. A., eds., A. R. Liss, New York, pp. 293–304.

  24. Garthwaite J. and Beaumont P. S. (1989) Excitatory amino acid receptors in the parallel fiber pathway in rat cerebellar slices.Neurosci. Lett. 107, 151–156.

  25. Gerber G. and Randic M. (1989a) Participation of excitatory amino acid receptors in the slow excitatory synaptic transmission in the rat spinal dorsal horn in vitro.Neurosci. Lett. 106, 220–228.

  26. Gerber G. and Randic M. (1989b) Excitatory amino acidmmediated components of synaptically evoked input from dorsal roots to deep dorsal horn neurons in the rat spinal cord slice.Neurosci. Lett. 106, 211–219.

  27. Grillner S., McClellan A., Sigvardt K., Wallen P., and Wilen M. (1981) Activation of NMDA-receptors elicits “fictive locomotion” in lamprey spinal cord in vitro.Acta Physiol. Scand. 113, 549–551.

  28. Henley C. M. and Igarashi M. (1991) Amino acid assay of vestibular nuclei 10 months after unilateral labyrinthectomy in squirrel monkeys.Acta Otolaryngologica Suppl. 481, 407–410.

  29. Hornfeldt C. S. and Larson A. A. (1989) Selective inhibition of excitatory amino acids by divalent cations. A novel means for distinguishingN-methyl-d-aspartic acid-, kainate-and quisqualate-mediated actions in the mouse spinal cord.J. Pharmacol. Exp. Therap. 251, 1064–1068.

  30. Ito J., Matsuoka I., Sasa M., Fujimoto S., and Takaori S. (1981) Electrophysiological evidence for involvement of acteylchloine as a neurotransmitter in the lateral vestibular nucleus.Otolaryngol. Head/Neck Surg. 89, 1023–1029.

  31. Jansen K. L. R., Fauli R. L. M., Dragunow M., and Waldvogel H. (1990) Autoradiographic localisation of NMDA, quisqualate and kainic acid receptors in human spinal cord.Neurosci. Lett. 108, 53–57.

  32. Kaneko T., Itoh K., Shigemoto R., and Mizuno N. (1989) Glutaminase-like immunoreactivity in the lower brainstem and cerebellum of the adult rat.Neuroscience 32, 79–98.

  33. Kano M. and Kato M. (1987) Quisqualate receptors are specifically involved in cerebellar synaptic plasticity.Nature 325, 276–279.

  34. Kessler J. P., Cherkaoui N., Catalin D., and Jean A. (1990) Swallowing responses induced by microinjection of glutamate and glutamate agonists into the nucleus tractus solitarius of ketamine-anesthetized rats.Exp. Brain Res. 83, 151–158.

  35. Knopfel T. (1987) Evidence forN-methyl-d-aspartic acid receptor-mediated modulation of the commissural input to central vestibular neurons of the frog.Brain Res. 426, 212–224.

  36. Knopfel T. and Dieringer N. (1988) Lesion-induced vestibular plasticity in the frog: areN-methyl-d-aspartate receptors involved?Exp. Brain Res. 72, 129–134.

  37. Kubo T. and Kihara M. (1988) Evidence ofN-methyl-d-aspartate receptor mediated modulation of the aortic baroreceptor reflex in the rat nucleus tractus solitarii.Neurosci. Lett. 87, 69.

  38. Larson-Prior L. J., McCrimmon D. R., and Slater N. T. (1990) Slow excitatory amino acid receptor-mediated synaptic transmission in turtle cerebellar Purkinje cells.J. Neurophysiol. 63, 637–650.

  39. Lewis M. R., Callagher J. P., and Shinnick-Gallagher P. (1987) An in vitro brain slice preparation to study the pharmacology of central vestibular neurons.J. Pharmacol. Methods 18, 267–273.

  40. Lewis M. R., Phelan K. D., Shinnick-Gallagher P., and Gallagher J. P. (1989) Primary afferent excitatory transmission recorded intracellularly in vitro from rat medial vestibular neurons.Synapse 3, 149–153.

  41. Lisberger S. (1988) The neural basis for learning of simple motor skills.Science.242, 728–735.

  42. Long S. K., Smith D. A. S., Siarey R. J., and Evans R. H. (1990) Effect of 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) on dorsal root-, NMDA-, kainate-and quisqualate-mediated depolarization of rat motoneurones in vitro.Br. J. Pharmacol. 100, 850–854.

  43. Luneburg U. and Flohr H. (1990) Possible role of NMDA receptors in vestibular compensation, inBrain-Perception Cognition, Elsner N. and Roth G., eds., Thieme, Stuttgart, p. 178.

  44. MacDermott A. B., Mayer M. L., Westbrook G. L., Smith S. J., and Barker J. L. (1986) NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones.Nature 321, 519–522.

  45. Matsuoka, I., Ito J., Takahashi H., Sasa M., and Takaori S. (1985) Experimental vestibular pharmacology: a minreview with special reference to neuroactive substances and antivertigo drugs.Acta Otolaryngol., Suppl.419, 62–70.

  46. Monaghan D. T. and Beaton J. A. (1991) Quinolinate differentiates between forebrain and cerebellar NMDA receptors.Eur. J. Pharmacol. 194, 123–125.

  47. Monaghan D. T. and Cotman C. W. (1985) Distribution ofN-methyl-d-aspartate-sensitivel-[3H] Glutamate-binding sites in rat brain.J. Neurosci. 5, 2909–2919.

  48. Murase K., Randic M., Shirasaki T., Nakagawa T., and Akaike N. (1990) Serotonin suppressesN-methyl-d-aspartate responses in acutely isolated spinal dorsal horn neurons of the rat.Brain Res. 525, 84–91.

  49. Nakagawa T., Shirasaki T., Tateishi N., Murase K., and Akaike N. (1990) Effects of antagonists onN-methyl-d-aspartate in acutely isolated nucleus tractus solitarii neurons of the rat.Neurosci Lett. 113, 169–174.

  50. Nehls D. G., Park C. K., MacCormack A. G., and McCulloch J. (1990) The effects ofN-methyl-d-aspartate receptor blockade with MK801 upon the relationship between cerebral blood flow and glucose utilisation.Brain Res. 511, 271–279.

  51. Ohta Y. and Grillner S. (1989) Monosynaptic excitatory amino acid transmission from the posterior rhombencephalic reticular nucleus to spinal neurons involved in the control of locomotion in the lamprey.J. Neurophysiol 62, 1079–1089.

  52. Ouardouz M. and Durand J. (1991) GYKI 52466 antagonizes glutamate responses but not NMDA and kainate responses in rat abducens motoneurones.Neurosci. Lett. 125, 5–8.

  53. Ozawa S., Precht W., and Shimazu H. (1974) Crossed effects on central vestibular neurons in the horizontal canal system of the frog.Exp. Brain Res. 19, 394–405.

  54. Pettorossi V. E., Della Torre G., Grassi S., Errico P., and Zampolini M. (1990) Role of NMDA receptors in oculomotor system plasticity.Neurosci. Lett. Suppl. 39, S169.

  55. Polc P. (1987) NMDA receptors mediate background and excessive activity of gamma motoneurons in the spinal cord.Eur. J. Pharmacol. 144 113.

  56. Precht W., Schwindt P. C., and Baker R. (1973) Removal of vestibular commissural inhibition by antagonists of GABA and glycine.Brain Res. 62, 222–226.

  57. Prigioni I., Russo G., Valli P., and Masetto S. (1990) Pre- and postsynaptic excitatory action of glutamate agonists on frog vestibular receptors.Hear. Res. 46, 253–259.

  58. Raigorodsky G. and Urca G. (1990) Spinal antinociceptive effects of excitatory amino acid antagonists: quisqualate modulates the action ofN-methyl-d-aspartate.Eur. J. Pharmacol. 182, 37–47.

  59. Raymond J. and Desmadryl G. (1985) In vitro effects of excitatory amino acid analogues on embryonic and newborn mouse inner ear structures.Soc. Neurosci. Abstr. 11, 448.

  60. Raymond J., Touati J., and Dememes D. (1989) Changes in the glutamate binding sites in the rat vestibular nuclei following hemilabyrinthectomy.Soc. Neurosci Abstr. 15, 518.

  61. Raymond J., Dememes D., and Nieoullon A. (1988) Neurotransmitters in vestibular pathways, inProg. Brain Res., vol. 76, Ponpeiano O. and Allum J. H. J., eds., Elsevier, Amsterdam, pp. 29–43.

  62. Raymond J., Nieoullon A., Dememes D., and Sans A. (1984) Evidence for glutamate as a neurotransmitter in the cat vestibular nerve: radioautographic and biochemical studies.Exp. Brain Res. 56, 523–531.

  63. Sansom A. J., Darlington C. L., and Smith P. F. (1990) Intraventricular injection of anN-methyl-d-aspartate antagonist disrupts vestibular compensation.Neuropharmacol. 29, 83, 84.

  64. Sansom A. J., Smith P. F., and Darlington C. L. The effects of excitatory amino acid antagonists on ocular motor and postural behavior in the guinea pig (in preparation).

  65. Schramm M., Eimerl S., and Costa E. (1990) Serum and depolarizing agents cause acute neurotoxicity in cultured cerebellar granule cells: role of the glutamate receptor responsive toN-methyl-d-aspartate.Proc. Natl. Acad. Sci. USA. 87, 1193–1197.

  66. Serafin M., Khateb A., de Waele C., Vidal P. P., and Muhlethaler M. (1990) Low threshold calcium spikes in medial vestibular nuclei neurones in vitro: a role in the generation of the vestibular nystagmus quick phase in vivo?Exp. Brain Res. 82, 187–190.

  67. Serafin M., Khateb A., de Waele C., Vidal P. P., and Muhlethaler M. (1991a) Oscillatory activity induced by NMDA and apamin in the medial vestibular nuclei.Experientia. 47, A11.

  68. Serafin M., de Waele C., Khateb A., Vidal P. P., and Muhlethaler M. (1991b) Medial vestibular nucleus in the guinea pig: I. Intrinsic membrane properties in brainstem slices.Exp. Brain Res. 84, 417–425.

  69. Serafin M., de Waele C., Khateb A., Vidal P. P., and Muhlethaler M. (1991c) Medial vestibular nucleus in the guinea pig: II. Ionic basis of the intrinsic membrane properties in brainstem slices.Exp. Brain Res. 84, 426–434.

  70. Shimazu H. (1983) Neuronal organization of the premotor system controlling horizontal conjugate eye movements and vestibular nystagmus.Motor Control Mechanisms in Health and Disease. Desmedt J. E., ed., Raven, New York, pp. 565–588.

  71. Shimazu H. and Precht W. (1965) Tonic and kinetic responses of cat's vestibular neurons to horizontal angular acceleration.J. Neurophysiol. 28, 991–1013.

  72. Shimazu H. and Precht H. (1966) Inhibition of central vestibular neurons from the contralateral labyrinth and its mediating pathway.J. Neurophysiol. 29, 467–492.

  73. Shirasaki T., Nakagawa T., Wakamori M., Tateishi N., Fukuda A., Murase K., and Akaike N. (1990) Glycine-insensitive desensitization ofN-methyl-d-aspartate receptors in acutely isolated mammalian central neurons.Neurosci. Lett. 108, 93–98.

  74. Sirkin D. W., Precht W., and Courjon J. H. (1984) Initial, rapid phase of recovery from unilateral vestibular lesion in rat not dependent on survival of central portion of vestibular nerve.Brain Res. 302, 245–256.

  75. Smith S. S. (1989) Quisqualate andN-methyl-d-aspartate synergistically excite cerebellar Purkinje cells as a long-term effect.Neurosci. Lett. 107, 63–69.

  76. Smith P. F. and Curthoys I. S. (1988) Neuronal activity in the ipsilateral medial vestibular nucleus of the guinea pig following unilateral labyrinthectomy.Brain Res. 444, 308–319.

  77. Smith P. F. and Curthoys I. S. (1989) Mechanisms of recovery following unilateral labyrinthectomy.Brain Res. Revs. 14, 155–180.

  78. Smith P. F. and Darlington C. L. (1988) The NMDA antagonists MK801 and CPP disrupt compensation for unilateral labyrinthectomy in the guinea pig.Neurosci. Lett. 94, 309–313.

  79. Smith P. F. and Darlington C. L. (1992) The effects ofN-methyl-d-aspartate (NMDA) receptor antagonists on vestibular compensation in the guinea pig: in vivo and in vitro studies.The Head-Neck Sensory-Motor System. Berthoz A., Graf W., and Vidal P. P., eds., Oxford University Press, New York, pp. 631–635.

  80. Smith P. F. and Darlington C. L. (1991) Neurochemical mechanisms of recovery from peripheral vestibular lesions (vestibular compensation).Brain Res. Revs. 16, 117–133.

  81. Smith P. F., Darlington C. L., and Hubbard J. I. (1990) Evidence that NMDA receptors contribute to synaptic function in the guinea pig medial vestibular nucleus.Brain Res. 513, 149–151.

  82. Sorimachi M., Nishimura S., and Kuramoto K. (1991) Receptor types mediating the rise in the cytosolic free calcium concentration byl-aspartate andl-glutamate in immature cerebellar neurons withN-methyl-d-aspartate receptors.Brain Res. 543, 166–169.

  83. Stein P. S. G. and Schild C. P. (1989)N-methyl-d-aspartate antagonist applied to the spinal cord hindlimb enlargement reduces the amplitude of flexion reflex in the turtle.Brain Res. 479, 379.

  84. Sundaram K. and Sapru H. (1991) NMDA receptors in the intermediolateral column of the spinal cord mediate sympathoexcitatory cardiac responses elicited from the ventrolateral medullary pressor area.Brain Res. 544, 33–41.

  85. Tell F. and Jean A. (1990) Rhythmic bursting patterns induced in neurons of the rat nucleus tractus solitarii, in vitro, in response toN-methyl-d-aspartate.Brain Res. 533, 152–156.

  86. Touati J., Raymond J., and Dememes D. (1989) Quantitative autoradiographic characterization ofl-[3H] glutamate binding sites in rat vestibular nuclei.Exp. Brain Res. 76, 646–650.

  87. Turski L., Bressler K., Klockgether T., and Stephens D. N. (1990) Differential effects of the excitatory amino acid antagonists, 6-cyno-7-nitroquinoxaline-2,3-dione (CNQX) and 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), on spinal reflex activity in mice.Neurosci. Lett. 113, 66–71.

  88. Ujihara H., Akaike A., Sasa M., and Takaori S. (1988) Electrophysiological evidence for cholinoceptive neurons in the medial vestibular nucleus: studies on rat brainstem in vitro.Neurosci. Lett. 93, 231–235.

  89. Valli P., Zucca G., Prigioni I., Botta L., Casella C., and Guth P. (1985) The effect of glutamate on the frog semicircular canal.Brain Res. 330, 1–9.

  90. White G., Lovinger D. M., and Weight F. F. (1990) Ethanol inhibits NMDA-activated current in an isolated adult mammalian neuron.Brain Res. 507, 332–336.

  91. Wilson V. J. and Melvill Jones G. (1979)Mammalian Vestibular Physiology. Plenum, New York.

  92. Wood P. L., Emmett M. R., Rao T. S., Mick S., Cler J., Oei E., and Iyengar S. (1990) In vivo antagonism of agonist actions atN-methyl-d-aspartate-associated glycine receptors in mouse cerebellum: studies of 1-hydroxy-3-aminopyrrolidone-2.Neuropharmacol. 29, 675–679.

  93. Ziskind-Conhaim L. (1990) NMDA receptors mediate poly-and monosynaptic potentials in motoneurons of rat embryos.J. Neurosci. 10, 125–135.

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Smith, P.F., de Waele, C., Vidal, P. et al. Excitatory amino acid receptors in normal and abnormal vestibular function. Mol Neurobiol 5, 369 (1991).

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Index Entries

  • Excitatory amino acid receptors
  • N-methyl-d-aspartate
  • lesion-induced plasticity
  • vestibular system
  • vestibular compensation