Learning and memory are fundamental components of how animals and humans navigate their world and adjust to environmental changes. These changes can include social interactions, which have particular importance for social animals, including humans. However, the neural basis of social learning is poorly understood. In order to uncover the specific neurochemicals and even individual neurons responsible for this memory, a tractable model system is necessary. The fruit fly, Drosophila melanogaster, is a premier genetic model organism with a large molecular genetic toolkit and has proven successful in establishing the molecules, brain regions, and in some cases individual neurons, responsible for conditioned memory. Indeed serotonin, dopamine, and octopamine have all be associated with various types of learning and memory. In anatomical studies, brain regions including the mushroom bodies, central complex, and lateral horn are important for learning and memory. The approach taken in this proposal is to apply these techniques to fruit fly fighting and the establishment of dominance relationships, which can serve as a social model of learning. Males fight over food and mates often forming dominance relationships. Following even a single fight, losers are likely to lose subsequent fights and fight at lower intensity against familiar than unfamiliar opponents, thus developing a """"""""loser mentality."""""""" Previous work has shown that the loser mentality persists for at least 24 hours, but the duration of this memory and whether it has a protein synthesis requirement remain unknown. Furthermore, the neurons responsible for consolidation of this memory have not been identified. This system represents an ideal one to test whether serotonin or small groups of serotonergic neurons are responsible for memory consolidation in the loser mentality. Further studies will address whether dopaminergic or octopaminergic neurons affect learning and memory. To accomplish these goals three specific aims are proposed: (1) to characterize the type of memory involved in the formation of the loser mentality using behavioral tests, pharmacology, and genetic drivers;(2) to test whether serotonin modulation affects memory consolidation using a combinatorial genetic approach;and (3) to identify and manipulate restricted populations of serotonergic or other aminergic neurons that modulate memory consolidation using intersectional genetics. If specific neurons are identified that are responsible for memory consolidation, potential synaptic connectivity can begin to be identified using a split gfp (GRASP, GFP Reconstruction Across Synaptic Partners). The proposed research has the potential to identify the specific neurons and neurochemicals responsible for the consolidation of memory in a loser mentality. Furthermore, this work will advance fruit fly aggression as a novel model for understanding socially-induced learning and identifying the neural basis of behavior.

Public Health Relevance

Human learning and memory is complex and often occurs in social environments. To gain a thorough understanding of the molecular and cellular basis of social learning we need a tractable model organism, and the fruit fly (Drosophila melanogaster) presents an ideal system to identify the neural basis of social learning through dominance relationships. The neurotransmitters involved in learning and memory, which include serotonin, are highly conserved between humans and insects suggesting that insights gained from this work will inform our understanding of learning and memory in all organisms.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Hoodbhoy, Tanya
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Harvard Medical School
Schools of Medicine
United States
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