Skip to main content
SpringerLink
Log in

Neurotoxicity of kainic acid in the rat cochlea during early developmental stages

  • Original Investigations
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Summary

The neurotoxic effect of kainic acid (KA) was investigated by electron microscopy in rat cochleas at two developmental stages: 17 days of gestation (17 G) and postnatal day 1 (PN 1). In each animal, one cochlea was injected with 1 nmol KA diluted into 2 ml artificial perilymph, while the other cochlea was only injected with artificial perilymph as a control. Ten minutes later, the cochleas were perfused with fixative, removed and processed for electron microscopy. The KA injection resulted in marked swelling of the majority of afferent fibers, i.e. the peripheral processes of spiral ganglion neurons. In the 17 G cochlea, swollen fibers were traced from the perikarya to the undifferentiated otocyst epithelium. Following birth, swollen afferents in the PN 1 cochlea were in contact with both inner (IHCs) and outer hair cells (OHCs), which were now differentiated. At both stages of development, a subclass of small afferent nerves were unaffected. At PN 1, the KA-insensitive afferents only contacted the OHCs. These fibers probably belong to the spiral system of afferents and are related to type II spiral ganglion cells. Conversely, KA-sensitive afferents probably belong to the radial system, related to type I spiral ganglion cells. This system is specific for IHCs in adult cochleas and appears to innervate both IHCs and OHCs at early developmental stages. These findings also indicate that KA neurotoxicity appears very early in the cochlea, at a prenatal time (17 G) before the presynaptic partners of afferent terminals (namely the IHCs) are differentiated. Thus, the neurotoxicity caused seems to be mediated via receptors located on the postsynaptic fiber and is widely distributed, as an immediate effect is visualized along the entire length of the unmyelinated peripheral afferent neurite.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Berglund A-M, Ryugo DK (1987) Hair cell innervation by spiral ganglion neurons in the mouse. J Comp Neurol 255:560–570

    Google Scholar 

  2. Biziere K, Coyle JT (1978) Influence of cortico-striatal afferents on striatal kainic acid neurotoxicity. Neurosci Lett 8:303–310

    Google Scholar 

  3. Biziere K, Coyle JT (1979) Localization of receptors for kainic acid on neurons in the innernuclear layer of retina. Neuropharmacology 18:409–413

    Google Scholar 

  4. Bledsoe SC, Bobbin RP, Chihal DM (1981) Kainic acid: an evaluation of its action on cochlear potentials. Hear Res 4: 109–120

    Google Scholar 

  5. Bobbin RP, Bledsoe SC, Jenison GL (1984) Neurotransmitters of the cochlea and lateral line organ. In: Berlin CI (ed) Hearing science. College Hill Press, San Diego, pp 159–180

    Google Scholar 

  6. Campana H, Suburo A (1986) The effect of kainic acid on the developing chick retina. Dev Brain Res 26:315–317

    Google Scholar 

  7. Campochiaro P, Coyle JT (1978) Ontogenetic development of kainate neurotoxicity: correlates with glutamatergic innervation. Proc Natl Acad Sci USA 75:2025–2029

    Google Scholar 

  8. Choi DW (1987) Ionic dependence of glutamate neurotoxicity. J Neurosci 7:369–379

    Google Scholar 

  9. Clough RW, Rodriguez-Sierra JF, Hoppe LB (1986) Kainic acid lesioning of the preoptic area alters positive feedback of estrogen in prepubertal female rats. Biol Reprod 35:1269–1276

    Google Scholar 

  10. Collins GGS, Anson J, Surtees L (1983) Presynaptic kainate and N-methyl-D-aspartate receptors regulate excitatory amino acid release in the olfactory cortex. Brain Res 265:157–159

    Google Scholar 

  11. Coyle JT (1983) Neurotoxic action of kainic acid. J Neurochem 41:1–11

    Google Scholar 

  12. Dallos P, Santos-Sacchi J, Flock A (1982) Intracellular recordings from cochlear outer hair cells. Science 218:582–584

    Google Scholar 

  13. Eybalin M, Pujol R (1983) A radioautographic study of [3H]Lglutamate and [3H]L-glutamane uptake in the guinea pig cochlea. Neuroscience 9:863–872

    Google Scholar 

  14. Ferkany JW, Zaczek R, Coyle JT (1982) Kainic acid stimulates excitatory amino-acid neurotransmitter release at presynaptic receptors. Nature 298:757–759

    Google Scholar 

  15. Franck JE, Schwartzkroin PA (1984) Immature rabbit hippocampus is damaged by systemic but not intraventricular kainic acid. Dev Brain Res 13:219–227

    Google Scholar 

  16. Garthwaite J, Garthwaite G (1983) The mechanism of kainic acid neurotoxicity. Nature 305: 138–140

    Google Scholar 

  17. Garthwaite G, Garthwaite J (1986) In vitro neurotoxicity of excitatory acid analogues during cerebellar development. Neuroscience. 17:755–767

    Google Scholar 

  18. Garthwaite G, Wilkin GP (1982) Kainic acid receptors and neurotoxicity in adult and immature rat cerebellar slices. Neuroscience 7:2499–2514

    Google Scholar 

  19. Gibson BL, Reif-Lehrer L (1984) In vitro effects of kainate on embryonic and posthatching chick retina. Dev Brain Res 15: 97–103

    Google Scholar 

  20. Herndon RM, Coyle JT, Addicks E (1980) Ultrastructural analysis of kainic acid lesion to cerebellar cortex. Neuroscience 5:1015–1026

    Google Scholar 

  21. Iurato S (1974) Efferent innervation of the cochlea. In: Keidel WD, Neff WD (eds) Auditory system, anatomy- physiology (ear), vol V/1. Springer, Berlin Heidelberg New York, pp 261–282

    Google Scholar 

  22. Jenison GL, Winberg S, Bobbin RP (1986) Comparative actions of quisqualate and N-methyl-D-aspartate, excitatory amino acids agonists, on the guinea-pig cochlear potentials. Comp Biochem Physiol 84C:385–389

    Google Scholar 

  23. Juiz JM, Rueda J, Merchan JA (1989) The effects of kainic acid on the cochlear ganglion of the rat. Hear Res 40: 65–74

    Google Scholar 

  24. Kiang NYS, Rho JM, Northrop CC, Liberman MC, Ryugo DK (1982) Hair-cell innervation by spiral ganglion cells in adult cats. Science 217:175–177

    Google Scholar 

  25. Kleinschmidt J, Zucker CL, Yazulla S (1986) Neurotoxic action of kainic acid in the isolated toad and goldfish retina. I. Description of effects. J Comp Neurol 254:184–195

    Google Scholar 

  26. Lenoir M, Shnerson A, Pujol R (1980) Cochlear receptor development in the rat with emphasis on synaptogenesis. Anat Embryol 160:253–262

    Google Scholar 

  27. Lorente de No R (1937) Sensory endings in the cochlea. Laryngoscope 47:373–377

    Google Scholar 

  28. Malthe-Sorenssen D, Odden E, Walaas I (1980) Selective destruction by kainic acid of neurons innervated by putative glutamatergic afferents in septum and nucleus of the diagonal band. Brain Res 182:461–465

    Google Scholar 

  29. Mayer ML, Westbrook GL (1987) Cellular mechanisms underlying excitotoxicity. Trends Neurosci 10:59–61

    Google Scholar 

  30. Olney JW (1978) Neurotoxicity of excitatory amino acids. In: McGeer EG, Olney JW, McGeer PL (eds) Kainic acid as a tool in neurobiology. Raven Press, New York, pp 201–218

    Google Scholar 

  31. Perkins RE, Morest DK (1975) A study of cochlear innervation patterns in cat and rat with the Golgi method and Nomarski optics. J Comp Neurol 163:129–158

    Google Scholar 

  32. Pujol R (1986) Synaptic plasticity in the developing cochlea. In: Ruben RW, Van de Water TR, Rubel EW (eds) The biology of change in otolaryngology. Elsevier, New York, pp 47–54

    Google Scholar 

  33. Pujol R, Abonnenc M (1977) Receptor maturation and synaptogenesis in the golden hamster cochlea. Arch Otorhinolaryngol 217:1–12

    Google Scholar 

  34. Pujol R, Carlier E, Devigne C (1978) Different patterns of cochlear innervation during the development in the kitten. J Comp Neurol 117:529–536

    Google Scholar 

  35. Pujol R, Lenoir M, Robertson D, Eybalin M, Johnstone BM (1985) Kainic acid selectivity alters auditory dendrites connected with cochlear inner hair cells. Hear Res 18: 145–151

    Google Scholar 

  36. Pujol R, Gil-Loyzaga P, Lenoir M (1987) Distribution of the two types of afferent dendrite in the developing cochlea: a kainic acid study. 10th A. R. O. Midwinter Research Meeting, Clearwater Beach, Fla., p 155

  37. Represa A, Tremblay E, Ben-Ari Y (1987) Kainate binding sites in the hippocampal mossy fibers: localization and plasticity. Neuroscience 20:739–748

    Google Scholar 

  38. Retzius G (1892) Die Endigungsweise des Gehörnerven. Biol Untersuch 3:29–36

    Google Scholar 

  39. Rothman SM (1985) The neurotoxicity of excitatory amino acids is produced by passive chloride influx. J Neurosci 5: 1483–1489

    Google Scholar 

  40. Rothman SM, Thurston JH, Hauhart RE (1987) Delayed neurotoxicity of excitatory amino acids in vitro. Neuroscience 22:471–480

    Google Scholar 

  41. Rueda J, Sen C de la, Ruiz JM, Merchan JA (1987) Neuronal loss in the spiral ganglion of young rats. Acta Otolaryugol (Stockh) 104:417–421

    Google Scholar 

  42. Russell IJ, Sellick PM (1983) Low frequency characteristics of intracellularly recorded receptor potentials in guinea pig cochlear hair cells. J Physiol 338:179–206

    Google Scholar 

  43. Santos-Sacchi J (1988) Cochlear physiology. In: Jahn AF, Santos-Sacchi J (eds) Physiology of the ear. Raven Press, New York, pp 271–293

    Google Scholar 

  44. Shnerson A, Devigne C, Pujol R (1982) Age-related changes in the C57B1/6J mouse cochlea. II. Ultrastructural findings. Dev Brain Res 2:77–78

    Google Scholar 

  45. Spoendlin H (1972) Innervation densities of the cochlea. Acta Otolaryngol (Stockh) 73:235–248

    Google Scholar 

  46. Vincent SR, McGeer EG (1979) Kainic acid binding to membranes of striatal neurons. Life Sci 24:265–270

    Google Scholar 

  47. Voukelatou G, Angelatoy F, Kouvelas ED (1986) The binding properties and regional ontogeny for [3H]glutamic acid Na+-independent and [3H]kainic acid binging sites in chick brain. Int J Dev Neurosci 4:339–352

    Google Scholar 

  48. Yazulla S, Kleinschmidt J (1980) The effects of intraocular injection of kainic acid on the synaptic organization of the goldfish retina. Brain Res 182:287–301

    Google Scholar 

  49. Young AMJ, Crowder JM, Bradford HF (1988) Potentiation by kainate of excitatory amino acid release in striatum: complementary in vivo and in vitro experiments. J Neurochem 50:337–345

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire Neurobiologie de l'Audition, INSERM - U. 254 et Université de Montpellier II, Hôpital St. Charles, F-34059, Montpellier Cedex, France

    P. Gil-Loyzaga & R. Pujol

  2. Department of Morphological Sciences, Universidad Complutense, Apdo 60075, E-28080, Madrid, Spain

    P. Gil-Loyzaga

Authors
  1. P. Gil-Loyzaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Pujol
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gil-Loyzaga, P., Pujol, R. Neurotoxicity of kainic acid in the rat cochlea during early developmental stages. Eur Arch Otorhinolaryngol 248, 40–48 (1990). https://doi.org/10.1007/BF00634780

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00634780

Key words

Search

Navigation