Abstract by Yantong Yang

Social behavior is a vital form of interaction in the animal kingdom, which is crucial for survival and reproduction. Aggressive and courtship behaviors are two innate and complex social behaviors. Among neurotransmitters and neuropeptides, serotonin (5-HT) is a classic neurotransmitter, being involved in a repertoire of complex behaviors. Here we investigate how the complex neural network of the 5-HT system plays a role in social behaviors, including courtship and aggressive behavior.

The proximal goal of courtship behavior is successful mating, which is tightly regulated in both males and females. In Drosophila, the receptivity of the female fly plays a decisive role in the success of mating. But how the 5-HT system controls female receptivity is still largely unknown. We found that the male-derived sex peptide (SP) reduces the activity of 5-HT SPN neurons in virgin females, and further decreases female receptivity. In addition, we evaluated the 5-HT7 receptor neurons for their important roles in the receptivity of virgin females. Silencing 5-HT7 receptor neurons in virgin females resulted in a very low copulation success, due to both the decreased courtship attempts in males and the reduced pausing frequency and increased ovipositor extrusion in females. The structural and functional experiments showed that 5-HT7 receptor neurons in GNG and superior medial protocerebrum (SMP) regions are downstream of SPN neurons to mediate SP signals. Together, the SP-SPN-5-HT7A signaling pathway controls virgin female receptivity in Drosophila.

Animals engage in aggressive behavior to obtain resources, and one such important resource is food. But how food controls aggression is still largely unknown. Hunger derived from food deprivation induces a range of behavioral changes. We established a paradigm of food deprivation in Drosophila, and found food deprivation could induce aggression in grouped flies. After a small screen, a line R19F09-Gal4 was identified. Activating or silencing R19F09 neurons increased or decreased aggressive levels, respectively. We found that Diuretic Hormone 31(DH31) functions in R19F09 neurons to modulate aggression. Surprisingly, 2 pairs of R19F09 neurons in the central brain are sufficient to control aggression. Additionally, the DH31R neurons (labeled by R23H02) are downstream of DH31 neurons. Activating approximately 4 pairs of DH31R neurons elevated aggression. Furthermore, starvation increased the activity of DH31 neurons, whereas silencing DH31 neurons blocked the elevated aggression induced by starvation. Last but not least, starvation increased the activity of 5-HT neurons as well, which function upstream of DH31 neurons to control aggression. Together, a 5-HT-DH31-DH31R axis mediates starvation-induced aggression in Drosophila.

5-HT and Calcitonin gene-related peptide (CGRP) both are well known in regulating vascular tone and targets on treating migraine. It was reported that 5-HT levels in the dorsal raphe nucleus (DR), the largest serotonergic nucleus, increase following peripheral CGRP levels, and CGRP receptors mRNA were colocalized in DR neurons. Therefore, we wanted to know whether CGRP plays a direct role and what are the cellular effects of CGRP on serotonergic DR neurons. By performing whole-cell patch clamp recording in DR brain slices, we found that CGRP elicited membrane responses in most 5-HT DR cells and the majority of the responding cells induced outward currents involving a postsynaptic mechanism and a potential role of potassium channel. In addition, we found that excitatory postsynaptic currents (EPSCs) in these cells who elicited outward currents less frequently. Through calcium imaging, we found CGRP also affected calcium dynamics in 5-HT DR cells, with the majority of DR cells showing a decrease in intracellular calcium. Pharmacological treatment with the CGRP agonist SAX replicated these effects. In contrast, the CGRP receptor antagonist MK3207 blocked the effects on outward current and decreased calcium signaling. However, CGRP had no overall change in the firing rate of DR cells. Take together, CGRP acts directly on CGRP receptors of DR neurons, and raise the intriguing possibility that the CGRP system plays a role in mediating emotional and social behaviors, at least in part through actions on serotonergic DR neurons.

In summary, I investigated three distinct neural circuits that control 5-HT signaling, which plays a role in regulating social behaviors.