Neural control of aggression in Drosophila Eric D Hoopfer Like most animal species, fruit flies fight to obtain and defend resources essential to survival and reproduction. Aggressive behavior in Drosophila is genetically specified and also strongly influenced by the fly’s social context, past experiences and internal states, making it an excellent framework for investigating the neural mechanisms that regulate complex social behaviors. Here, I summarize our current knowledge of the neural control of aggression in Drosophila and discuss recent advances in understanding the sensory pathways that influence the decision to fight or court, the neuromodulatory control of aggression, the neural basis by which internal states can influence both fighting and courtship, and how social experience modifies aggressive behavior. Address Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Blvd. M/C156-29, Pasadena, CA, United States Corresponding author: Hoopfer, Eric D (hoopfere@caltech.edu) Current Opinion in Neurobiology 2016, 38:109–118 This review comes from a themed issue on Neurobiology of sex Edited by Barry Dickson and Catherine Dulac http://dx.doi.org/10.1016/j.conb.2016.04.007 0959-4388/# 2016 Elsevier Ltd. All rights reserved. Introduction Aggression is essential for survival and reproduction in most animal species [1]. It consists of a complex repertoire of social interactions aimed at gaining or defending resources, territory and mates. Males display an innate ability to engage in aggression, suggesting that the devel- opment and function of the circuits underlying aggression are genetically hardwired. Aggressive behavior is also strongly modulated by external sensory information, past social experiences and the internal state of the animal. Thus, aggression represents an ideal paradigm for inves- tigating the neural mechanisms underlying how these different influences drive behavioral decisions. Despite the ethological importance of aggression, we still under- stand relatively little about the neural circuits that under- lie this behavior. For example, what are neural circuits that mediate aggression? How are these circuits function- ally organized in the brain, and how do they interact with circuits for closely related social behaviors like courtship and mating? How do external cues and internal motiva- tional or drive states act on these circuits to modify this goal-directed behavior [2  ,3]? The common fruit fly, Drosophila melanogaster, has prov- en to be a valuable system for understanding the genetic and neural underpinnings of social behaviors like court- ship [reviewed in [4,5]]. In contrast to the study of courtship, it was not until relatively recently that Drosophila gained ground as a model for investigating aggression, due in part to the development of simplified behavior assays for obtaining robust aggression between pairs of male flies [6–8]. Since then increasing attention has been focused on investigating the genetic and neural mechanisms that regulate Drosophila aggression [reviewed in [9,10]]. This review focuses on our current understanding of the neural control of aggressive behav- ior in Drosophila, highlighting recent advances in the identification of specific neural populations underlying aggressive behavior, how aggression and courtship beha- viors are coordinated, and how social experiences modify aggression. I conclude by discussing some directions for future research. A primer on aggression in Drosophila Aggressive flies display a distinct set of agonistic behaviors (for a detailed description see [6]; Figure 1a). Detailed descriptions of the sequence of behaviors during agonistic interactions between pairs of males or females [6,11] indi- cate that unlike the relatively ordered progression of courtship, aggression involves a more complex structure of recurring behavioral sequences. Similar to courtship behavior, the early stages of agonistic interactions involve orientation and approach towards the other fly, exchange of chemosensory information through touching of the fore- legs (fencing) and visual displays (wing flicking and wing threat). Fights often escalate to higher-intensity physical interactions (lunging, tussling and boxing), which are thought to serve in establishing territorial dominance [11,12]. Females display aggressive behavior as well, how- ever the vigor and types of agonistic behaviors differs from males [11,13  ]. The expression of these sexually dimorphic levels and patterns of aggression requires the action of sex- specific transcripts of fruitless ( fru) [13  ], which acts as a master regulator of sexual differentiation of the brain [14]. The role of fru in specifying both male courtship and aggressive behavior suggests that the circuits underlying these behaviors are likely to be highly intertwined. Indeed, several recently identified neuronal populations that regu- late aggression express the male isoform of Fru (Fru M ) (see Table 1). Available online at www.sciencedirect.com ScienceDirect www.sciencedirect.com Current Opinion in Neurobiology 2016, 38:109–118