Publication Date

2018

Document Type

Dissertation/Thesis

First Advisor

Wallace, Douglas G.

Degree Name

M.A. (Master of Arts)

Legacy Department

Department of Psychology

LCSH

Neurosciences; Cognitive psychology

Abstract

Usher syndrome is an autosomal recessive disorder that results in impaired visual, auditory and vestibular function. In mouse models, Usher syndrome manifests itself through abnormal behaviors such as circling, poor auditory brainstem responses, and a decline in harmonin expression. Animals utilize several sources of information to guide spatial navigation (e.g., visual cues, vestibular input). Usher syndrome disrupts these essential sensory modalities. Recent work has demonstrated that an antisense oligonucleotide (ASO) therapy can attenuate the auditory deficit of Usher syndrome through an increase in harmonin production and correct splicing. However, it has yet to be determined if this therapy can also rescue vestibular function and the impaired spatial orientation that is associated with vestibular pathologies. The current study examines the effect of Usher syndrome and an ASO therapy on the organization of exploratory movements under dark and light testing conditions. Heterozygous and mutant Usher mice received an infusion of ASO or a control infusion at postnatal day five. At two-months of age, mouse exploratory behavior was recorded for 50 minutes during three consecutive dark sessions followed by three consecutive light sessions. Motion capture software was used to segment the movement paths into progressions and stops, which was utilized to determine exploratory movement organization. Mutant Usher mice demonstrated irregular exploratory movements compared to heterozygous mice. The ASO therapy attenuated these disruptions in exploratory movement organization. These results demonstrate the potential for an ASO therapy to ameliorate spatial orientation deficits associated with Usher syndrome. Further research is needed to assess the effectiveness of ASO therapy at different time points following treatment and to characterize the effects of ASO therapy on neural systems that mediate exploratory movement organization.

Comments

Advisor: Wallace, Douglas.||Committee members: Grippo, Angela; Hastings, Michelle; Matuszewich, Leslie.||Includes bibliographical references.

Extent

68 pages

Language

eng

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

Media Type

Text

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