Auditory brainstem neural activation patterns are altered in EphA4- and ephrin-B2-deficient mice

Ilona J. Miko, Paul A. Nakamura, Mark Henkemeyer, Karina S. Cramer

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Auditory processing requires proper formation of tonotopically ordered projections. We have evaluated the role of an Eph receptor tyrosine kinase and an ephrin ligand in the development of these frequency maps. We demonstrated expression of EphA4 and ephrin-B2 in auditory nuclei and found expression gradients along the frequency axis in neonates. We tested the roles of EphA4 and ephrin-B2 in development of auditory projections by evaluating whether mutations result in altered patterns of expression of the immediate early gene c-fos after exposure to pure tone stimuli. We evaluated two nuclei, the dorsal cochlear nucleus (DCN) and the medial nucleus of the trapezoid body (MNTB), which project in two distinct auditory pathways. The mean number of c-fos-positive neurons in EphA4-/- DCN after 8-kHz pure tone stimulation was 42% lower than in wild-type DCN. Along the dorsoventral, tonotopic axis of DCN, the mean position of c-fos-positive neurons was similar for mutant and wild-type mice, but the spread of these neurons along the tonotopic axis was 35% greater for ephrin-B2lacZ/+ mice than for wild-type mice. We also examined these parameters in MNTB after exposure to 40-kHz pure tones. Both EphA4-/- and ephrin-B2lacZ/+ mice had significantly fewer c-fos-positive cells than wild-type littermates. The labeled band of cells was narrower and laterally shifted in EphA4-/- mice compared with wild-type mice. These differences in cell number and distribution suggest that EphA4 and ephrin-B2 signaling influence auditory activation patterns.

Original languageEnglish (US)
Pages (from-to)669-681
Number of pages13
JournalJournal of Comparative Neurology
Volume505
Issue number6
DOIs
StatePublished - Dec 20 2007

Fingerprint

Ephrin-B2
Brain Stem
Cochlear Nucleus
Ephrins
Neurons
Eph Family Receptors
Auditory Pathways
Immediate-Early Genes
Cell Count
Ligands
Mutation

Keywords

  • Auditory
  • Brainstem
  • c-fos
  • Development
  • Eph receptor
  • Ephrin
  • Tonotopy
  • Topography

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Auditory brainstem neural activation patterns are altered in EphA4- and ephrin-B2-deficient mice. / Miko, Ilona J.; Nakamura, Paul A.; Henkemeyer, Mark; Cramer, Karina S.

In: Journal of Comparative Neurology, Vol. 505, No. 6, 20.12.2007, p. 669-681.

Research output: Contribution to journalArticle

Miko, Ilona J. ; Nakamura, Paul A. ; Henkemeyer, Mark ; Cramer, Karina S. / Auditory brainstem neural activation patterns are altered in EphA4- and ephrin-B2-deficient mice. In: Journal of Comparative Neurology. 2007 ; Vol. 505, No. 6. pp. 669-681.
@article{00fb4fa7b9fd44cbacaad1362b70d62f,
title = "Auditory brainstem neural activation patterns are altered in EphA4- and ephrin-B2-deficient mice",
abstract = "Auditory processing requires proper formation of tonotopically ordered projections. We have evaluated the role of an Eph receptor tyrosine kinase and an ephrin ligand in the development of these frequency maps. We demonstrated expression of EphA4 and ephrin-B2 in auditory nuclei and found expression gradients along the frequency axis in neonates. We tested the roles of EphA4 and ephrin-B2 in development of auditory projections by evaluating whether mutations result in altered patterns of expression of the immediate early gene c-fos after exposure to pure tone stimuli. We evaluated two nuclei, the dorsal cochlear nucleus (DCN) and the medial nucleus of the trapezoid body (MNTB), which project in two distinct auditory pathways. The mean number of c-fos-positive neurons in EphA4-/- DCN after 8-kHz pure tone stimulation was 42{\%} lower than in wild-type DCN. Along the dorsoventral, tonotopic axis of DCN, the mean position of c-fos-positive neurons was similar for mutant and wild-type mice, but the spread of these neurons along the tonotopic axis was 35{\%} greater for ephrin-B2lacZ/+ mice than for wild-type mice. We also examined these parameters in MNTB after exposure to 40-kHz pure tones. Both EphA4-/- and ephrin-B2lacZ/+ mice had significantly fewer c-fos-positive cells than wild-type littermates. The labeled band of cells was narrower and laterally shifted in EphA4-/- mice compared with wild-type mice. These differences in cell number and distribution suggest that EphA4 and ephrin-B2 signaling influence auditory activation patterns.",
keywords = "Auditory, Brainstem, c-fos, Development, Eph receptor, Ephrin, Tonotopy, Topography",
author = "Miko, {Ilona J.} and Nakamura, {Paul A.} and Mark Henkemeyer and Cramer, {Karina S.}",
year = "2007",
month = "12",
day = "20",
doi = "10.1002/cne.21530",
language = "English (US)",
volume = "505",
pages = "669--681",
journal = "Journal of Comparative Neurology",
issn = "0021-9967",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Auditory brainstem neural activation patterns are altered in EphA4- and ephrin-B2-deficient mice

AU - Miko, Ilona J.

AU - Nakamura, Paul A.

AU - Henkemeyer, Mark

AU - Cramer, Karina S.

PY - 2007/12/20

Y1 - 2007/12/20

N2 - Auditory processing requires proper formation of tonotopically ordered projections. We have evaluated the role of an Eph receptor tyrosine kinase and an ephrin ligand in the development of these frequency maps. We demonstrated expression of EphA4 and ephrin-B2 in auditory nuclei and found expression gradients along the frequency axis in neonates. We tested the roles of EphA4 and ephrin-B2 in development of auditory projections by evaluating whether mutations result in altered patterns of expression of the immediate early gene c-fos after exposure to pure tone stimuli. We evaluated two nuclei, the dorsal cochlear nucleus (DCN) and the medial nucleus of the trapezoid body (MNTB), which project in two distinct auditory pathways. The mean number of c-fos-positive neurons in EphA4-/- DCN after 8-kHz pure tone stimulation was 42% lower than in wild-type DCN. Along the dorsoventral, tonotopic axis of DCN, the mean position of c-fos-positive neurons was similar for mutant and wild-type mice, but the spread of these neurons along the tonotopic axis was 35% greater for ephrin-B2lacZ/+ mice than for wild-type mice. We also examined these parameters in MNTB after exposure to 40-kHz pure tones. Both EphA4-/- and ephrin-B2lacZ/+ mice had significantly fewer c-fos-positive cells than wild-type littermates. The labeled band of cells was narrower and laterally shifted in EphA4-/- mice compared with wild-type mice. These differences in cell number and distribution suggest that EphA4 and ephrin-B2 signaling influence auditory activation patterns.

AB - Auditory processing requires proper formation of tonotopically ordered projections. We have evaluated the role of an Eph receptor tyrosine kinase and an ephrin ligand in the development of these frequency maps. We demonstrated expression of EphA4 and ephrin-B2 in auditory nuclei and found expression gradients along the frequency axis in neonates. We tested the roles of EphA4 and ephrin-B2 in development of auditory projections by evaluating whether mutations result in altered patterns of expression of the immediate early gene c-fos after exposure to pure tone stimuli. We evaluated two nuclei, the dorsal cochlear nucleus (DCN) and the medial nucleus of the trapezoid body (MNTB), which project in two distinct auditory pathways. The mean number of c-fos-positive neurons in EphA4-/- DCN after 8-kHz pure tone stimulation was 42% lower than in wild-type DCN. Along the dorsoventral, tonotopic axis of DCN, the mean position of c-fos-positive neurons was similar for mutant and wild-type mice, but the spread of these neurons along the tonotopic axis was 35% greater for ephrin-B2lacZ/+ mice than for wild-type mice. We also examined these parameters in MNTB after exposure to 40-kHz pure tones. Both EphA4-/- and ephrin-B2lacZ/+ mice had significantly fewer c-fos-positive cells than wild-type littermates. The labeled band of cells was narrower and laterally shifted in EphA4-/- mice compared with wild-type mice. These differences in cell number and distribution suggest that EphA4 and ephrin-B2 signaling influence auditory activation patterns.

KW - Auditory

KW - Brainstem

KW - c-fos

KW - Development

KW - Eph receptor

KW - Ephrin

KW - Tonotopy

KW - Topography

UR - http://www.scopus.com/inward/record.url?scp=37049003498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37049003498&partnerID=8YFLogxK

U2 - 10.1002/cne.21530

DO - 10.1002/cne.21530

M3 - Article

VL - 505

SP - 669

EP - 681

JO - Journal of Comparative Neurology

JF - Journal of Comparative Neurology

SN - 0021-9967

IS - 6

ER -