Abstract
Vestibular compensation is the process of behavioral recovery that occurs following unilateral deafferentation of the vestibular nerve fibers (unilateral labyrinthectomy, UL). Since UL results in a permanent loss of vestibular input from the ipsilateral vestibular (VIIIth) nerve, vestibular compensation is attributed to CNS plasticity and has been used as a general model of lesion-induced CNS plasticity. Behavioral recovery from the ocular motor and postural symptoms of UL is correlated with a partial return of resting activity to neurons in the vestibular nucleus (VN) on the deafferented side (the “deafferented VN”), and lesions to the deafferented VN prevent compensation; therefore, the regeneration of resting activity within the deafferented VN is believed to have a causal role in vestibular compensation. The biochemical mechanisms responsible for the adaptive neuronal changes within the deafferented VN are poorly understood. Neuropeptide hormone fragments, such as adrenocorticotrophic hormone (ACTH)-4–10, have been shown to accelerate vestibular compensation and can act directly on some VN neurons in vitro. Antagonists for theN-methyl-D-aspartate (NMDA) receptor have been shown to inhibit vestibular compensation if administered early in the compensation process. Biochemical studies in frog indicate marked alterations in the phosphorylation patterns of several proteins during compensation, and the in vitro phosphorylation of some of these proteins is modulated by ACTH-(1–24), calcium (Ca2+), and calmodulin or protein kinase C. It is therefore possible that ACTH fragments and NMDA antagonists (via their effects on NMDA receptor-mediated Ca2+ channels) modulate vestibular compensation through their action on Ca2+-dependent pathways within VN neurons. Recent studies have shown that some Ca2+-channel antagonists and the Ca2+-dependent enzyme inhibitor calmidazolium chloride facilitate vestibular compensation. How the regulation of Ca2+ may be related to the neuronal changes responsible for vestibular compensation is unclear at present.
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References
Bienhold H. and Flohr H. (1978) Role of commissural connections between vestibular nuclei in compensation following unilateral labyrinthectomy.J. Physiol. (Lond.) 248, 178P.
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.
Collingridge G. L. and Bliss T. V. P. (1987) NMDA receptors—their role in long term potentiation.Trends Neurosci. 10, 288–293.
Collingridge G. L. and Singer W. (1990) Excitatory amino acid receptors and synaptic plasticity.Trends Pharmacol Sci. 11, 290–296.
Darlington C. L. and Smith P. F. (1989) The effects of NMDA antagonists on the development of vestibular compensation in the guinea pig.Eur. J. Pharmacol. 174, 273–278.
Darlington C. L. and Smith P. F. (1991a) Behavioral recovery from peripheral vestibular lesions as a model of recovery from brain damage.New Zealand J. Psychol. 20, 25–32.
Darlington C. L. and Smith P. F. (1991b) Verapamil accelerates the disappearance of spontaneous nystagmus following inner ear lesions in the guinea pig.Proc. Univ. Otago Med Sch. 69, 15, 16.
Darlington C. L. and Smith P. F. The effects of pretreatment with verapamil on compensation for peripheral vestibular deafferentation in the guinea pig (in preparation).
Darlington C. L., Smith P. F., and Hubbard J. I. (1989) Neuronal activity in the guinea pig medial vestibular nucleus in vitro following chronic unilateral labyrinthectomy.Neurosci. Lett. 105, 143–148.
Darlington C. L., Smith P. F., and Hubbard, J. L. (1990) Guinea pig medial vestibular nucleus neurons in vitro respond to ACTH-(4–10) at picomolar concentration.Exp. Brain Res. 82, 637–640.
de Waele C., Serafin M., Muhlethaler M., and Vidal P. P. (1988) Vestibular compensation: an in vivo and in vitro study of second order vestibular neurons.Soc. Neurosci. Abstr. 14, 331.
de Waele C., Graf W., Josset P., and Vidal P. P. (1989a) A radiological analysis of the postural syndromes following hemilabyrinthectomy and selective canal and otolith lesions in the guinea pig.Exp. Brain Res. 77, 166–182.
de Waele C., Serafin M., Muhlethaler M., and Vidal P. P. (1989b) 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.
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 hemilabyrinthectomized guinea pig.Exp. Brain Res. 81, 125–133.
Dieringer N. and Precht W. (1977) Modification of synaptic input following unilateral labyrinthectomy.Nature 269, 431–433.
Dieringer N. and Precht W. (1979) Mechanism of compensation for vestibular deficits in the frog. 1. Modification of the excitatory commissural system.Exp. Brain Res. 36, 311–328.
Doroshenko P. A., Kostyuk P. K., and Luk'yaetz, E. A. (1988) Modulation of calcium current by calmodulin antagonists.Neurosci. 27, 1073–1090.
Finger S., Green L., Tarnoff N. E., Mortman K. D., and Andersen A. (1990) Nimodipine enhances new learning after hippocampal damage.Exp. Neurol. 109, 279–285.
Fisch U. (1973) The vestibular response following unilateral vestibular neurectomy.Acta Otolaryngol 76, 229–238.
Flohr H. and Luneburg U. (1982) Effects of ACTH-(4–10) on vestibular compensation.Brain Res. 248, 169–173.
Flohr H. and Luneburg U. (1989) Influence of melanocortin fragments on vestibular compensation, inVestibular Compensation: Facts, Theories And Clinical Perspectives, Lacour M., Toupet M., Denise P., and Christen Y. eds., Elsevier, Paris, pp. 161–174.
Flohr H., Luneburg U., and Richter-Landsberg C. (1985) ACTH/MSH-like neuropeptides and lesion-induced plastic processes.Adaptive Processes in Visual and Oculomotor Systems. Keller E. L. and Zee D. S., eds., Pergamon, Oxford, pp. 405–416.
Flohr H., Bienhold H., Abeln W., and Macskovics I. (1981) Concepts of vestibular compensation.Lesion-Induced Neuronal Plasticity, in Sensorimotor Systems. Flohr H. and Precht W., eds., Springer, Amsterdam, pp. 153–172.
Flohr H., Burt A., Will U., and Ammelburg R. (1989) Vestibular compensation: a paradigm for lesion-induced neural plasticity.Fundamentals of Memory Formation: Neuronal Plasticity and Brain Function. Rahmann, R., ed., Springer, Stuttgart, pp. 243–260.
Frank G. B. (1986) A pharmacological explanation of the use-dependency of the verapamil (and D-600) block of slow calcium channels.J. Pharmacol. Exp. Therap. 236, 505–511.
Gilchrist D. P. D., Darlington C. L., and Smith P. F. Comparison of the effects of adrenocorticotrophic hormone, fragment 4–10 (ACTH-(4–10)) and [D-Phe7]ACTH-(4–10) on the compensation of spontaneous nystagmus in the guinea pig.Retorative Neurology and Neuroscience (in press).
Gilchrist D. P. D., Smith P. F. and Darlington C. L. (1990) ACTH(4–10) accelerates ocular motor recovery in the guinea pig following vestibular-deafferentation.Neuroscience Letters 118, 14–16.
Halmagyi G. M., Curthoys I. S., Cremer P. D., Henderson C. J., Todd M. J., Staples M. J., and D'Cruz D. M. (1990) The human horizontal vestibulo-ocular reflex in response to high-acceleration stimulation before and after unilateral vestibular neurectomy.Exp. Brain Res. 81, 479–490.
Hamann K.-F. and Lannou J. (1988) Dynamic characteristics of vestibular nuclear neurons responses to vestibular and optokinetic stimulation during vestibular compensation in the rat.Acta Otolaryngol. Suppl. 445, 1–19.
Henley C. M., and Igarashi M. (1990) Amino acid assay of vestibular nuclei 10 months after unilateral labyrinthectomy in squirrel monkeys.Acta Otolaryngol. Suppl. 481, 407–410.
Igarashi M., Watanabe T., and Maxian P. M. (1970) Dynamic equilibrium in squirrel monkeys after unilateral and bilateral labyrinthectomy.Acta Otolaryngologica 96, 247–253.
Igarashi M., Ishii M., Ishikawa K., and Himi T. (1988) Comparative effect of some neurotropic agents on balance compensation after unilateral and bilateral (two-staged) labyrinthectomy in squirrel monkeys.Post-Lesion Neural Plasticity, Flohr H., ed., Springer, Berlin, pp. 627–634.
Igarashi M., Ishikawa K., Ishii M., and Schmidt K. A. (1985) Effect of ACTH-(4–10) on equilibrium compensation after unilateral labyrinthectomy in the squirret monkey.European Journal of Pharmacology,119, 239–242.
Ishii M. and Igarashi M. (1987) Effect of ACTH-(4–10) on Bechterew's compensation in squirrel monkeys.ORL 49, 87–92.
Ito M. (1982) Cerebellar control of the vestibulo-ocular reflex around the flocculus hypothesis.An.. Rev. Neurosci. 5, 275–296.
Iyengar S., Mick S., Dilworth V., Michel J., Rao T. S., Farah J. M., and Wood P. L. (1990) Sigma receptors modulate the hypothalamic-pituitary-adrenal (HPA) axis centrally: evidence for a functional interaction with NMDA receptors, in vivo.Neuropharmacol. 29, 299–303.
Janssen U., Richter-Landsberg C., and Flohr H. (1987) Vestibular compensation stimulates Ca++/calmodulin dependent phosphorylation of myelin basic protein.New Frontiers in Brain Research. Elsner N. and Creutzfeldt O., eds., Thieme, Stuttgart, p. 285.
Janssen U., Richter-Landsberg C., and Flohr H. (1988) Lesion-induced changes in the phosphorylation pattern of frog brain proteins.Eur. J. Neurosci. Suppl. 211, 31.
Janssen U., Oestreicher A. B., DeGraan P. N. E., Gispen W. H., Richter-Landsberg C., and Flohr H. (1989) Modulation of a B-50-like synaptosomal phosphoprotein during vestibular compensation of Rana Temporaria.Dynamics and Plasticity in Neuronal Systems. Elsner N. and Singer W., eds., Thieme, Stuttgart, p. 263.
Jensen D. W. (1983) Survival of function in the deafferented vestibular nerve.Brain Res. 273, 175–178.
Kjerulf T. D. and Loeser J. D. (1973) Neuronal hyperactivity following deafferentation of the lateral cuneate nucleus.Exp. Neurol. 39, 70–85.
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.
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.
Linden D. J., Wong K. L., Sheu F. S., and Routenberg A. (1988) NMDA receptor blockade prevents the increase in protein kinase C substrate (protein F1) phosphorylation produced by long term potentiation.Brain Res. 458, 142–146.
Lisberger S. G. (1988) The neural basis for learning of simple motor skills.Science 242, 728–735.
Llinas R. R. and Walton K. (1979) Vestibular compensation: a distributed property of the central nervous system.Integration in the Nervous Systems. Asanuma H. and Wilson V. J., eds., Igaku-Shon, Tokyo, pp. 145–166.
Luneburg U. and Flohr H. (1988) Effects of melanocortins on vestibular compensation.Progress in Brain Research, vol. 76. Pompeiano O. and Allum J. H. J., eds., Elsevier, Amsterdam, pp. 421–429.
Luneburg U. and Flohr H. (1990) Possible role of NMDA receptors in vestibular compensation.Brain-Perception Cognition. Elsner N. and Roth G., eds., Thieme, Stuttgart, p. 178.
Luyten W. H. M. L., Sharp F. R., and Ryan A. F. (1986) Regional differences of brain glucose metabolic compensation after unilateral labyrinthectomy in rats: a [14C] 2-deoxyglucose study.Brain Res. 373 68–80.
Maeda M. (1988) Investigation of compensatory mechanisms in the hemilabyrinthectomized cat by means of neurochemical approaches.Prog. Brain Res., vol. 76, Vestibulospinal Control of Posture and Movement. Pompeiano O. and Allum J. H. J., eds., Elsevier, Amsterdam, pp. 385–394.
Maioli C., Precht W., and Ried S. (1983) Short- and long-term modification of vestibulo-ocular response dynamics following unilateral vestibular nerve lesions in the cat.Exp. Brain Res. 50, 259–274.
Mazzei G. J., Schatzman R. C., Turner R. S., Vogler W. R., and Kuot J. F. (1984) Phospholipid-sensitive Ca2+-dependent protein kinase inhibition by R24571, a calmodulin antagonist.Biochem. Pharmacol 33, 125–130.
McCabe B. F. and Ryu J. H. (1969) Experiments on vestibular compensation.Laryngoscope 79, 1728–1736.
McCabe B. F., Ryu J. H., and Sekitani T. (1972) Further experiments on vestibular compensation.Laryngoscope 82, 381–396.
Needleman P., Corr P. B., and Johnson E. M., Jr. (1985) Drugs used for the treatment of angina: organic nitrates, calcium channel blockers and beta-adrenergic antagonists.The Pharmacological Basis of Therapeutics. Goodman Gilman A., Goodman L. S., Rall T. W., and Murad F., eds., MacMillan, New York, pp. 806–826.
Newlands S. D. and Perachio A. (1986) Effects of commissurotomy on vestibular compensation in the gerbil.Soc. Neurosci. Abstr. 12, 254.
Newlands S. D. and Perachio A. (1987) Vestibular commissures in the gerbil.Soc. Neurosci. Abstr. 13, 634.
Newlands, S. D. and Perachio A. (1990) Compensation of horizontal canal related activity in the medial vestibular nucleus following unilateral labyrinth ablation in the decerebrate gerbil.Exp. Brain Res. 82, 359–372.
Pettorossi V. E., Della Torre G., Grassi S., Errico P., and Zampolini M. (1990) Role of NMDA receptors in oculomotor plasticity.Neurosci. Lett.,Suppl. 39, S169.
Pohorecki R., Becker G. L., Reilly P. J., and Landers D. F. (1990) Ischemic brain injury in vitro: protective effects of NMDA receptor antagonists and calmidazolium.Brain Res. 528, 133–137.
Pompeiano O., Xerri C., Gianni S., and Manzoni D. (1984) Central compensation of vestibular deficits. II. Influences of roll tilt on different size lateral vestibular neurons after ipsilateral labyrinth deafferentation.J. Neurophysiol. 52, 18–38.
Precht W. and Dieringer N. (1985) Neuronal events paralleling functional recovery (compensation) following peripheral vestibular lesions.Adaptive Mechanisms in Gaze Control. Facts and Theories. Berthoz A. and Melvill Jones G., eds., Elsevier, Amsterdam, pp. 251–268.
Precht W., Shimazu H., and Markham C. H. (1966) A mechanism of central compensation of vestibular function following hemilabyrinthectomy.J. Neurophysiol. 29, 996–1010.
Ried S. Maioli C., and Precht W. (1984) Vestibular nuclear neurons activity in chronically labyrinthectomized cats.Acta Otolaryngol. 98, 1–13.
Sansom A. J., Darlington C. L., and Smith P. F. (1990) Intraventricular injection of an NMDA antagonist disrupts vestibular compensation.Neuropharmacol. 29, 83,84.
Sansom A. J., Darlington C. L., Smith, P. F., Gilchrist D. P. D., and Keenan C. Intraventricular infection of calmidazolium chloride decreases spontaneous nystagmus following unilateral labyrinthectomy in the guinea pig (in preparation).
Serafin M., de Waele C., Khateb A., Vidal P.-P., and Muhlethaler M. (1991a) Medial vestibular nucleus in the guinea pig: I. Intrinsic membrane properties in brainstem slices.Exp. Brain Res. 84, 417–425.
Serafin M., de Waele C., Khateb A., Vidal P-P., and Muhlethaler M. (1991b) Medial vestibular nucleus in the guinea pig: II. Ionic basis of the intrinsic membrane properties in brainstem slices.Exp. Brain Res. 84, 426–434.
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.
Schuknecht H. F. (1982) Behavior of the vestibular nerve following labyrinthectomy.Otol. Rhinol. Laryngol. Suppl. 91, 16–32.
Sirkin D. W., Precht W., and Courjon J. H. (1984) Initial rapid phase of recovery from unilateral vestibular lesions in rat not dependent on survival of central portion of vestibular nerve.Brain Res. 302, 245–256.
Sitges M., Chiu L. M., and Ramon de la Fuente J. (1990) The effect of verapamil on GABA and dopamine release does not involve voltage-sensitive calcium channels.Brain Res. 534, 51–59.
Smith P. F. and Curthoys I. S. (1988a) Neuronal activity in the ipsilateral medial vestibular nucleus of the guinea pig following unilateral labyrinthectomy.Brain Res. 444, 308–319.
Smith P. F. and Curthoys I. S. (1988b) Neuronal activity in the contralateral medial vestibular nucleus of the guinea pig following unilateral labyrinthectomy.Brain Res. 444, 295–307.
Smith P. F. and Curthoys I. S. (1989) Mechanisms of recovery following unilateral labyrinthectomy.Brain Res. Revs. 14, 155–180.
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.
Smith P. F. and Darlington C. L. (1991) Neurochemical mechanisms of recovery from peripheral vestibular lesions (vestibular compensation).Brain Res. Revs.
Smith P. F., Darlington C. L. and Curthoys I. S. (1986a) The effect of visual deprivation on vestibular compensation in the guinea pig.Brain Res. 364, 195–198.
Smith P. F., Darlington C. L., and Curthoys I. S. (1986b) Vestibular compensation without brainstem commissures in the guinea pig.Neurosci. Lett. 65, 209–213.
Smith P. F., Darlington C. L., and Hubbard J. I. (1991) Evidence for inhibitory amino acid receptors on guinea pig medial vestibular nucleus neurons in vitro.Neurosci. Lett. 121, 244–246.
Spiegel E. A. and Demetriades T. D. (1925) Die zentrale compensation des laybrinthverlustes.Pflugers Arch. Ges. Physiol. 210, 215–222.
Strand F. L., Rose K. J., King J. A., Segarra A. C., and Zuccarelli L. A. (1989) ACTH modulation of nerve development and regeneration.Prog. Neurobiol. 33, 45–85.
Takahashi K. and Akaike N. (1991) Calcium antagonist effects on low-threshold (T-type) calcium current in rat isolated hippocampal CA1 pyramidal neurons.J. Pharmacol. Exp. Therap. 256, 169–175.
Thayer S. A. and Fairhurst A. S. (1983) The interaction of dihydropyridine Ca2+ channel blockers with calmodulin and calmodulin inhibitors.Mol. Pharmacol. 24, 6–9.
Tolu E., Mameli O., Caria M. A., and Melis, F. (1988a) Improvement of vestibular plasticity in the guinea pig with a calcium entry blocker.Acta Otolaryngol. Suppl. 460, 72–79.
Tolu E., Mameli O., Melis F., and Caria M. A. (1988b) Role of the Ca2+ entry blocker Flunarizine in vestibular compensation.Post-Lesion Neural Plasticity. Flohr H., ed., Springer, Berlin, pp. 687–698.
Van Belle H. (1981) R 24 571: a potent inhibitor of calmodulin-activated enzymes.Cell Calcium 2, 483–494.
Wilson V. J. and Melvill Jones G. (1979)Mammalian Vestibular Physiology. Plenum, New York.
Wolpaw J. R., Kieffer V. A., Seegal R. F., Braitman D. J., and Sanders M. G. (1983) Adaptive plasticity in the spinal stretch reflex.Brain Res. 267, 196–200.
Wu K., Wasterlain C., Sachs L., and Siekevitz P. (1990) Effect of septal kindling on glutamate binding and calcium/calmodulin-dependent phosphorylation in a postsynaptic density fraction isolated from rat cerebral cortex.Proc. Natl. Acad. Sci. USA. 87, 5298–5302.
Xerri C., Gianni S., Manzoni D., and Pompeiano O. (1983) Compensation of central vestibular deficits. 1. Response characteristics of lateral vestibular neurons to roll tilt after ipsilateral labyrinth deafferentation.J. Neurophysiol. 50, 428–448.
Zernig G. (1990) Widening potential for Ca2+ antagonists: non-L-type Ca2+ channel interaction.Trends Pharmacol. Sci. 11, 38–44.
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Darlington, C.L., Flohr, H. & Smith, P.F. Molecular mechanisms of Brainstem plasticity. Mol Neurobiol 5, 355–368 (1991). https://doi.org/10.1007/BF02935558
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DOI: https://doi.org/10.1007/BF02935558