Document Detail

Auditory brainstem neural activation patterns are altered in EphA4- and ephrin-B2-deficient mice.
MedLine Citation:
PMID:  17948875     Owner:  NLM     Status:  MEDLINE    
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-B2(lacZ/+) mice than for wild-type mice. We also examined these parameters in MNTB after exposure to 40-kHz pure tones. Both EphA4(-/-) and ephrin-B2(lacZ/+) 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.
Ilona J Miko; Paul A Nakamura; Mark Henkemeyer; Karina S Cramer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of comparative neurology     Volume:  505     ISSN:  0021-9967     ISO Abbreviation:  J. Comp. Neurol.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-10-25     Completed Date:  2008-01-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0406041     Medline TA:  J Comp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  669-81     Citation Subset:  IM    
Department of Neurobiology and Behavior, University of California Irvine, Irvine, California 92697, USA.
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MeSH Terms
Acoustic Stimulation
Auditory Pathways / abnormalities*,  cytology,  metabolism
Auditory Perception / genetics
Body Patterning / genetics*
Brain Stem / abnormalities*,  cytology,  metabolism
Cell Count
Cochlear Nucleus / abnormalities,  cytology,  metabolism
Ephrin-B2 / genetics*
Gene Expression Regulation, Developmental / genetics*
Mice, Knockout
Neurons / metabolism
Olivary Nucleus / abnormalities,  cytology,  metabolism
Proto-Oncogene Proteins c-fos / genetics
Receptor, EphA4 / genetics*
Grant Support
Reg. No./Substance:
0/Ephrin-B2; 0/Proto-Oncogene Proteins c-fos; EC, EphA4

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