Ephrin-A3 is required for tonotopic map precision and auditory functions in the mouse auditory brainstem.

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.

A New Source of Nonprofit Neurosurgical Funding.

The purpose of this paper is to propose and qualify a novel funding mechanism for international neurosurgical nonprofits. The article first identifies and explains neurosurgeons' means for practicing in the developing world through a literature review. After this examination of the current funding methods for surgical care in low-income regions, the work transitions to an explanation of the applications and limitations of a new resource: the internal wealth of a developing country. This wealth may be leveraged by way of a for-profit hospital to create sustainable and domestic funding for nonprofit neurosurgical training. The applicability of the proposed mechanism extends beyond the field of neurosurgery to nonprofits in any health-related discipline. Factors influencing the viability of this mechanism (including local disease burden, economic trajectory, and political stability) are examined to create a baseline set of conditions for success.