The role of ephrin-B3 on midbrain topography and auditory function

Abstract

Eph-ephrins are a family of molecular guidance proteins that provide cell-cell interactions necessary for topographic mapping and pattern formation in the developing nervous system. Studies in our laboratory have shown in mouse the transient expression of certain Eph-ephrin members in the developing inferior colliculus (IC) prior to hearing onset. Ephrin-B3 expression, while absent in the central nucleus (CNIC), is highly expressed in extramodular domains of the lateral cortex (LCIC) as well as the mesencephalic midline. We utilize multiple-labeling approaches in control and ephrin-B3 mutants to explore the development of converging CNIC and LCIC afferent patterns. Tract-tracing studies describe the relative distribution patterns of local and commissural CNIC connections together with an ascending input arising from the auditory brainstem. Additionally, we performed auditory brainstem responses (ABRs) as a physiological assessment of the auditory circuitry for each of our experimental groups. While tract-tracing experiments reveal no gross anatomical abnormalities between wild-type and ephrin-B3 mutants, ABRs show effects on auditory threshold, peak amplitude, and waveform fidelity in ephrin-B3 mutant mice. Taken together, these findings suggest that while ephrin-B3 may not influence the construction of topographic maps for the examined IC afferents, it is indeed necessary for ensuring fully functional auditory circuits prior to experience