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The pursuit of reproductive success exerts a significant evolutionary pressure that has played a pivotal role in shaping neural circuits responsible for controlling animal behavior. Males and females exhibit sexually dimorphic behaviors, mainly in sexual and social interactions. It is generally believed that these behavioral differences arise due to variations in how the sensory systems of males and females receive and process external and internal signals during social interactions. While the brain receives a diverse range of sensory inputs from both external and internal sources, molecular and neuronal mechanisms underlying sensory processing during social behaviors remain largely unknown. To understand how mating behaviors are implemented at the molecular and circuitry levels in the central nervous system, I use the fruit fly, Drosophila melanogaster courtship, and aggression behaviors as a model. Flies serve as a unique genetic model organism for these studies because male and female flies show sexually dimorphic behaviors, and the system offers genetic, molecular, and connectome access to specific cell types and their manipulation at the cellular level.Using a genome-wide neuronal RNAi screen dataset, I have identified a gene associated with mating behaviors, the Drosophila ortholog of the human GABAA-receptor-associated protein (GABARAP). GABARAP knockdown in the nervous system showed sexually dimorphic effects on fly behavior. In male flies, GABARAP knockdown increased male-male courtship behavior; in contrast, the same manipulation decreased receptivity and elevated aggression toward males in female flies. In the first part of my thesis, I investigated how GABARAP regulates male courtship behavior at the level of molecules and circuits. Through multiple genetic screens using various intersectional approaches, I identified visual feedback neurons called lamina tangential (Lat) neurons that regulate visually-guided male courtship behavior. Our sequence analysis and behavior experiments revealed that Drosophila and human GABARAPs are genetically and functionally homologous. Considering that the human GABARAP modulates the trafficking and synaptic localization of GABAA receptors, the Drosophila GABARAP might also have a similar function. In addition, supported by in vivo two-photon imaging coupled with optogenetics, I showed that Lat neurons are functionally connected to neural circuits that mediate visually-guided courtship pursuits in males. My work reveals a novel physiological role for GABARAP in fine-tuning the activity of a visual circuit that tracks a mating partner during courtship. I propose that GABARAP/GABAA receptor signaling maintains the activity of visual feedback neurons, Lat, at a precise level that allows males to court females but avoid males. The second part of my thesis focused on the role of GABARAP in regulating female receptivity and aggression. My subsequent behavioral and genetic analysis identified sexually dimorphic pC1 neurons, in which GABARAP knockdown elicited a significant reduction in female receptivity. My results demonstrated that GABARAP regulates male and female behavior via different populations of neurons; Lat in males and pC1 in females. Given that GABARAP is conserved across flies to humans, my thesis project provides insights into how GABARAP/GABAA receptor signaling modulates the activity of neural circuits that regulate social behaviors in flies and might help us better understand the molecular and neuronal mechanisms underlying social deficits seen in human psychiatric disorders.

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153 pages


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courtship behavior; Drosophila melanogaster; GABA receptor signaling; neural circuits


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Union Local


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Yapici, Nilay

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Committee Member

Warden, Melissa
Han, Chun
Bass, Andrew

Degree Discipline

Neurobiology and Behavior

Degree Name

Ph. D., Neurobiology and Behavior

Degree Level

Doctor of Philosophy

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Government Document




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Attribution-NonCommercial-NoDerivatives 4.0 International


dissertation or thesis

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