Single Serotonergic Neurons that Modulate Aggression in Drosophila

Monoamine serotonin (5HT) has been linked to aggression for many years across species [1-3]. However, elaboration of the neurochemical pathways that govern aggression has proven difficult because monoaminergic neurons also regulate other behaviors [4,5]. There are approximately 100 serotonergic neurons in the Drosophila nervous system, and they influence sleep [6], circadian rhythms [7], memory [8,9], and courtship [10]. In the Drosophila model of aggression [11], the acute shut down of the entire serotonergic system yields flies that fight less, whereas induced activation of 5HT neurons promotes aggression [12]. Using intersectional genetics, we restricted the population of 5HT neurons that can be reproducibly manipulated to identify those that modulate aggression. Although similar approaches were used recently to find aggression-modulating dopaminergic [13] and Fru(M)-positive peptidergic [14] neurons, the downstream anatomical targets of the neurons that make up aggression-controlling circuits remain poorly understood. Here, we identified a symmetrical pair of serotonergic PLP neurons that are necessary for the proper escalation of aggression. Silencing these neurons reduced aggression in male flies, and activating them increased aggression in male flies. GFP reconstitution across synaptic partners (GRASP) [15] analyses suggest that 5HT-PLP neurons form contacts with 5HT1A receptor-expressing neurons in two distinct anatomical regions of the brain. Activation of these 5HT1A receptor-expressing neurons, in turn, caused reductions in aggression. Our studies, therefore, suggest that aggression may be held in check, at least in part, by inhibitory input from 5HT1A receptor-bearing neurons, which can be released by activation of the 5HT-PLP neurons.