GENETIC REGULATION OF THE ACOUSTIC STARTLE THRESHOLD

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Degree type
Doctor of Philosophy (PhD)
Graduate group
Neuroscience
Discipline
Neuroscience and Neurobiology
Biology
Genetics and Genomics
Subject
acoustic sensitivity
behavioral thresholds
hypersensitivty
zebrafish
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Copyright date
01/01/2024
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Author
Ortiz, Elelbin
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Abstract

Animals have a challenging task while navigating their environment: they must continuously ignore irrelevant information while responding to important environmental cues. To achieve this task, animals must establish mechanisms to regulate their behavior in response to their environments. An approach animals can use is to use characteristics of a stimulus, such as the intensity, to determine if a behavioral response is required. The acoustic startle response is a highly conserved defensive behavior during which animals respond to sudden sounds if the sound intensity surpasses a threshold. Regulation of this threshold has two components: establishment of an innate baseline threshold during development and short-term modifications to the threshold based on acute changes in the environment. Dysregulation of the acoustic startle threshold is associated with several human neurodevelopmental and neuropsychiatric disorders. Despite its importance, the genetic mechanisms that underlie establishment of the startle threshold, and how these mechanisms overlap or diverge between establishment and acute regulation are poorly understood. Using a mutant zebrafish line (escapist), I identified a single base pair mutation that is tightly linked to an abnormally lowered baseline acoustic startle threshold. Using the mutation as a genetic tool to identify escapist mutants, I identify that escapist larvae exhibit changes in baseline responses to acoustic and visual stimuli. In contrast, further characterization of short-term regulation of acoustic and visual behavior thresholds identifies that acute regulation remains intact in escapist larvae compared to wildtype siblings. My work highlights the existence of nonoverlapping regulators of baseline and acute behavioral thresholds and provides an entry point to study the genetic and cellular mechanisms underlying the development of innate behavioral thresholds.

Advisor
Granato, Michael
Date of degree
2024
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