Senior Honors Projects, 2010-current

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Date of Award

Spring 2014

Document Type

Thesis

Degree Name

Bachelor of Science (BS)

Department

Department of Biology

Advisor(s)

Mark Gabriele

Janet Daniel

Justin Brown

Abstract

Processing of sophisticated auditory tasks requires complex circuitry in the brain. These pathways are highly organized, as central connections preserve and integrate stimulus attributes received from the periphery. The focus of our laboratory is centered upon understanding how central auditory connections develop prior to experience (postnatal day 12, P12 in mouse). The present study examines the establishment of projection maps from an auditory center in the brainstem, the lateral superior olivary nucleus (LSO), to the auditory midbrain or inferior colliculus (IC). Previous results from our lab show that LSO to IC projections are arranged tonotopically (i.e. frequency-mapped) before hearing onset, and subsequently these frequency- specific inputs segregate into characteristic axonal layers. Here we test the influence a signaling molecule, EphA4, exerts in establishing this early topography. The Eph family of receptor tyrosine kinases and the ephrin ligands are proteins that are involved in guiding the development of axonal targeting and topographic map formation in other systems. Comparatively less is known about their involvement in the development of the auditory system, particularly their role in the development of patterned inputs to the auditory midbrain. Recent studies reveal EphA4- positive LSO neurons as well as an EphA4 expression gradient along the IC tonotopic axis during the early developmental period when axonal layers emerge. Anterograde fluorescent tract-tracing approaches are used to compare the establishment of ordered LSO-IC projection patterns in wild-type and EphA4 mutants. We hypothesize that EphA4 signaling is necessary for accurate LSO point-to-point mapping and pattern formation in the IC prior to experience. Results indicate no qualitative errors in EphA4 mutants concerning the targeting ability of LSO projections to the IC and subsequent formation of characteristic axonal layers. These findings provide necessary insights regarding the role Eph-ephrin signaling plays in constructing complex auditory circuits prior to experience.

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