The Neuromodulatory Basis of Aggression: Lessons From the Humble Fruit Fly

Abstract

Aggression is an intrinsic trait that organisms of almost all species, humans included, use to get access to food, shelter, and mating partners. To maximize fitness in the wild, an organism must vary the intensity of aggression toward the same or different stimuli. How much of this variation is genetic and how much is externally induced, is largely unknown but is likely to be a combination of both. Irrespective of the source, one of the principal physiological mechanisms altering the aggression intensity involves neuromodulation. Any change or variation in aggression intensity is most likely governed by a complex interaction of several neuromodulators acting via a meshwork of neural circuits. Resolving aggression-specific neural circuits in a mammalian model has proven challenging due to the highly complex nature of the mammalian brain. In that regard, the fruit fly model Drosophila melanogaster has provided insights into the circuit-driven mechanisms of aggression regulation and its underlying neuromodulatory basis. Despite morphological dissimilarities, the fly brain shares striking similarities with the mammalian brain in genes, neuromodulatory systems, and circuit-organization, making the findings from the fly model extremely valuable for understanding the fundamental circuit logic of human aggression. This review discusses our current understanding of how neuromodulators regulate aggression based on findings from the fruit fly model. We specifically focus on the roles of Serotonin (5-HT), Dopamine (DA), Octopamine (OA), Acetylcholine (ACTH), Sex Peptides (SP), Tachykinin (TK), Neuropeptide F (NPF), and Drosulfakinin (Dsk) in fruit fly male and female aggression.

Keywords: Drosophila melanogaster; acetylcholine; aggression; dopamine; neuromodulator; octopamine; peptides; serotonin.

FIGURE 1

Motor programs used in fruit fly aggression. The Venn diagram shows the different motor programs used in male and female aggression. Some of the motor programs are sexually dimorphic. The motor programs encircled in blue are specific for male aggression. The motor programs encircled in red are specific to female aggression. The intersection enlists the motor programs common to both male and female aggression (A). The most consistent motor program in male aggression is a lunge (B). In a lunge, a male fly stands on its hind legs and snaps down on its opponent. The most consistent motor program in female aggression is a head butt. In a head butt, the female fly extends her torso and strikes the opponent with her head (C).

FIGURE 2

Connectivity graph of SAG neurons and pC1α neurons. SAG neurons project major inputs into the pC1α neurons. pC1α neurons make reciprocal connections within the pC1 neuronal cluster. Red lines indicate synaptic connections and the numbers within the arrows represent number of shared synapses. Arrows indicate putative target. Numbers underneath traced neurons indicate the ID number from the neuPrint server (https://neuprint.janelia.org/) (Zheng et al., 2018; Scheffer et al., 2020; Wang et al., 2020).