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Date of Graduation
5-11-2023
Document Type
Dissertation
Degree Name
Doctor of Audiology (AuD)
Department
Communication Sciences and Disorders
Advisor(s)
Lincoln Gray
Christopher Clinard
Erin Piker
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication, restricted behaviors, and executive functioning deficits. Mutations in fractalkine signaling, particularly in CX3CR1, in the brain have been linked to ASD and other neurodevelopmental disorders. This investigation examined wild-type mice and mice with one or two copies of mutated CX3CR1 and their uni-modal (auditory and somatosensory) and multi-modal (combined) pre-pulse inhibitions (PPI). PPI is an unconditioned response – a decrement in the acoustic startle reflex when the mouse detects a non-startling stimulus presented a few hundred ms before the startling sound. In this study, the pre-pulses were various combinations of noise and vibrations. Homozygous mice (mice with 2 copies of mutated CX3CR1) had significantly larger PPIs to both types of uni-modal stimuli than the wild-type and heterozygous mice, but all three groups had equivalent PPI with multi-modal pre-pulses. There was a significant effect of mutation on ‘synergy’, which was calculated as the sum of the uni-modal PPIs subtracted from the multi-modal PPI, so 0 synergy means the sum of separate responses (to auditory and somatosensory pre-pulses) equal the response to the simultaneous presentation of the two stimuli. Synergy in the wild-type mice was zero, suggesting near perfect multi-sensory integration, while synergy became increasingly more negative for heterozygous and homozygous mice, respectively, suggesting less efficient multi-sensory integration. As in ASD, the ‘neurodiverse’ mice were more responsive to simple stimuli but were less able to integrate stimuli. This is a possible animal model of a discrepancy in perceiving details vs an overall pattern.
Recommended Citation
Besser, Michelle, "The effect of microglial cell dysfunction on multi-modal pre-pulse inhibition" (2023). Dissertations, 2020-current. 111.
https://commons.lib.jmu.edu/diss202029/111
