Premium
Ephrin‐A3 is required for tonotopic map precision and auditory functions in the mouse auditory brainstem
Author(s) -
Hoshino Natalia,
Altarshan Yazan,
Alzein Ahmad,
Fernando Amali M.,
Nguyen Hieu T.,
Majewski Emma F.,
Chen Vincent C.F.,
Rochlin M. William,
Yu WeiMing
Publication year - 2021
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.25213
Subject(s) - tonotopy , brainstem , neuroscience , cochlea , auditory system , cochlear nucleus , biology , nucleus , sensory system , auditory pathways , axon guidance , erythropoietin producing hepatocellular (eph) receptor , axon , microbiology and biotechnology , signal transduction , receptor tyrosine kinase
Tonotopy is a prominent feature of the vertebrate auditory system and forms the basis for sound discrimination, but the molecular mechanism that underlies its formation remains largely elusive. Ephrin/Eph signaling is known to play important roles in axon guidance during topographic mapping in other sensory systems, so we investigated its possible role in the establishment of tonotopy in the mouse cochlear nucleus. We found that ephrin‐A3 molecules are differentially expressed along the tonotopic axis in the cochlear nucleus during innervation. Ephrin‐A3 forward signaling is sufficient to repel auditory nerve fibers in a developmental stage‐dependent manner. In mice lacking ephrin‐A3, the tonotopic map is degraded and isofrequency bands of neuronal activation upon pure tone exposure become imprecise in the anteroventral cochlear nucleus. Ephrin‐A3 mutant mice also exhibit a delayed second wave in auditory brainstem responses upon sound stimuli and impaired detection of sound frequency changes. Our findings establish an essential role for ephrin‐A3 in forming precise tonotopy in the auditory brainstem to ensure accurate sound discrimination.