Date of Award

Spring 2014

Document Type

Dissertation

Degree Name

Doctor of Audiology (AuD)

Department

Department of Communication Sciences and Disorders

Advisor(s)

Lincoln C. Gray

Brenda M. Ryals

Christopher G. Clinard

Abstract

The acoustic startle response (ASR) is a reliable reflexive behavioral response in mammals elicited by an unexpected intense acoustic startle eliciting stimulus (SES). It is mediated by a sub-cortical pathway that includes the inferior colliculus (IC). The ASR amplitude can be measured with an accelerometer beneath the subject attached to the cage, and can be decreased in amplitude by presenting a less intense, non-startling stimulus 20-300 ms before the SES. This reflexive decrement in ASR is called pre pulse inhibition (PPI) and indicates that the relatively soft pre pulse was heard. Murine species have been used to study this response for psychoacoustical estimates of hearing thresholds and to understand the effects of genetic mutations on the ASR, PPI and the afferent auditory neural pathway. The Eph/ephrin signaling pathway is known to be important in directing developing auditory afferents, including connections to various subdivisions of the IC. In this experiment, we measured the effect of Eph/ephrin mutations on PPI in mice with a control strain (C57BL/6J), a strain with compromised EphA4 signaling (EphA4lacZ), and a knockout ephrin-B3 strain (ephrin-B3null). The control strain and EphA4lacZ strain showed robust PPI (up to 75% decrement in ASR) to an offset of a 70dB SPLrms background noise at 50ms before the SES. Ephrin-B3 knockout mice were only marginally significant in PPI (< 25% decrement) to the same conditions. This reduction in PPI highlights the significance of ephrin-B3 in the developing afferent auditory system by ways of auditory behavioral measurement. Thus, different mutations for certain members of the Eph/ephrin signaling family produce a full range of changes in PPI, from minimal to nearly maximal. This technique can be easily adapted to study other aspects of hearing in a wider range of mutations. Along with ongoing neuroanatomical studies, this allows careful quantification of how the auditory anatomical, physiological and now behavioral phenotype is affected by changes in the Eph/ephrin genotype.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.