Date of Award

2023-08-01

Degree Name

Doctor of Philosophy

Department

Biological Sciences

Advisor(s)

Kyung-An Han

Abstract

Inhibitory control is an executive function suppressing inappropriate actions or thoughts and inhibitory control dysfunction leads to impulsivity. Impulsivity is associated with wide-ranging brain disorders including attention deficit hyperactivity disorder, autism spectrum disorder, substance use disorder, and dementia. The genetic and non-genetic factors contributing to impulsivity are poorly understood. This dissertation aims to begin closing this knowledge gap by identifying the genetic and non-genetic factors for impulsivity and the underlying mechanism in the model organism Drosophila melanogaster. For this task, we developed a new Go/No-Go test, which measures the fly's ability to suppress movements in situations that can endanger its safety or survival such as strong wind and predatory sound. When flies were unable to maintain movement suppression, they displayed impulsive flying behavior, which is inappropriate in a small chamber. In this dissertation work, I identified 3 major factors important for impulsivity. First, I identified nighttime caffeine as a key non-genetic factor for impulsivity. In the study, I also observed sex differences where caffeine-fed females displayed more severe impulsivity than caffeine-fed males. Furthermore, I identified dopamine signaling as a key cellular mechanism for caffeine-induced impulsivity. The second impulsivity factor I identified is the Shaker/KCNA voltage-gated potassium channel complex Shaker, Hyperkinetic, and quiver/sleepless. I further clarified the mushroom body lobe neurons as the neural site where the Shaker complex play a role in impulsivity. Lastly, through a functional genetic screen, I identified the novel genetic factor Kekkon5 that encodes a synaptic cell adhesion molecule. Kekkon5 caused impulsivity upon interaction with hyper dopamine. This dissertation is the first to uncover the aforementioned genetic and non-genetic factors as key contributors to impulsivity. This study may provide insights into how these factors contribute to impulsivity-related brain disorders and may lead to the development of preventive and therapeutic interventions.

Language

en

Provenance

Recieved from ProQuest

File Size

143 p.

File Format

application/pdf

Rights Holder

Erick Benjamin Saldes

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