Aggression is an innate behavior that is a nearly universal feature of the social behavior of animals. In the wild, it is used for access to food and shelter, for protection from predation and for selection of mates. Despite its importance little is known of the neural mechanisms that underlie the behavior. Over the past decade, we have developed a Drosophila melanogaster model of aggression. In same sex pairing of male and female flies, these animals will compete over resources. Males develop hierarchical relationships while females do not, and learning and memory take place during the male fights. A single gene, fruitless, specifies both how flies fight and who they court. Amines have been shown to be important in aggression in all species of animals examined thus far. Fruit flies are no exception. These studies focus on two major amines found in the fruit fly nervous system: octopamine (OA), the phenol analogue of norepinephrine, is the major amine synthesized from tyrosine;and serotonin (5HT), is the major amine derived from tryptophan. There are approximately 100 OA and 5HT neurons in the Drosophila central nervous system. Of the total OA pool, we have identified a small group of 3 or 4 neurons, that co-express the amine and the male protein forms of Fruitless (FruM/OA neurons). These appear to be involved in the decision made by male flies between courtship and aggression. Here we propose to use state of the art genetic methods and a combinatorial method to unravel the circuitry concerned with the FruM/OA neurons, from sensory input through to behavioral output. 5HT serve roles in aggression (not in initiating fights, but in bringing fights to higher intensity levels), courtship behavior, balance and feeding behavior in flies. We ask here whether we can identify the specific 5HT neurons involved in these behaviors, and then can map the circuitry involving the neuron or neurons concerned with aggression. The project has the following Specific Aims:
Aim 1 : To generate a data base of the morphological features and functional roles served by individual 5HT, OA and dopamine (DA) neurons.
Aim 2 : Selective manipulation of FruM/OA neurons and behavioral choice: can we map the circuitry concerned with these neurons.
Aim 3 : Selective manipulation of individual serotonergic neurons. Can we identify which of the ca. 100 5HT neurons are concerned with each of the behaviors known to be influenced by 5HT? If so, can we then map the circuitry involved with 5HT and aggression, the same way we plan to map the FruM/OA circuitry. Studies exploring the roles of amine neurons in behavior at this level of detail just are not possible with other model systems at the present time.

Public Health Relevance

All organisms, including humans, must be capable of rapidly evaluating social situations and of selecting proper responses from a wide variety of possible behavioral choices. Such selections must be correctly made to allow the survival of organisms as individuals or as a species. How organisms make such choices and how the underlying neural circuitry involved in decision making is constructed are the themes of this application.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Molecular Neurogenetics Study Section (MNG)
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Sesma, Michael A
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Harvard University
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Jois, Shreyas; Chan, Yick Bun; Fernandez, Maria Paz et al. (2018) Characterization of the Sexually Dimorphic fruitless Neurons That Regulate Copulation Duration. Front Physiol 9:780
Chowdhury, Budhaditya; Chan, Yick-Bun; Kravitz, Edward A (2017) Putative transmembrane transporter modulates higher-level aggression in Drosophila. Proc Natl Acad Sci U S A 114:2373-2378
Trannoy, Séverine; Penn, Jill; Lucey, Kenia et al. (2016) Short and long-lasting behavioral consequences of agonistic encounters between male Drosophila melanogaster. Proc Natl Acad Sci U S A 113:4818-23
Trannoy, Severine; Chowdhury, Budhaditya; Kravitz, Edward A (2015) A New Approach that Eliminates Handling for Studying Aggression and the ""Loser"" Effect in Drosophila melanogaster. J Vis Exp :e53395
Kravitz, Edward A; Fernandez, Maria de la Paz (2015) Aggression in Drosophila. Behav Neurosci 129:549-63
Trannoy, Severine; Kravitz, Edward A (2015) Learning and memory during aggression in Drosophila: handling affects aggression and the formation of a ""loser"" effect. J Nat Sci 1:e56
Chan, Yick-Bun; Alekseyenko, Olga V; Kravitz, Edward A (2015) Optogenetic Control of Gene Expression in Drosophila. PLoS One 10:e0138181
Trannoy, Severine; Chowdhury, Budhaditya; Kravitz, Edward A (2015) Handling alters aggression and ""loser"" effect formation in Drosophila melanogaster. Learn Mem 22:64-8
Andrews, Jonathan C; Fernández, María Paz; Yu, Qin et al. (2014) Octopamine neuromodulation regulates Gr32a-linked aggression and courtship pathways in Drosophila males. PLoS Genet 10:e1004356
Alekseyenko, Olga V; Kravitz, Edward A (2014) Serotonin and the search for the anatomical substrate of aggression. Fly (Austin) 8:200-5

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