View Program - 63rd Annual Drosophila Research Conference

Certain perceptive experiences, such as the sudden death of a companion or repeated exposure to traumatic events, have significant behavioral and physiological effects that are well established across taxa. Recently, we demonstrated that when Drosophila melanogaster perceive dead conspecifics in their environment, they exhibit behavioral and physiological changes that influence energy metabolism, stress resistance, and lifespan. Sight and serotonin signaling through receptor 5-HT2A are required for these effects to manifest upon exposure to dead. New data using neural tracing and genetic analyses identified the ellipsoid body, a neuropil in the central complex that is known to be important for multifaceted sensory integration and motor coordination functions, as an important structure underlying the effects of death perception on lifespan. To better understand how this structure transduces perceptual experience into physiological changes, we dissected the contributions of individual ellipsoid body ring neurons and found that activity of the R4d and R4m neurons were required for the effect of death perception on lifespan. To elucidate the molecular mechanisms, we executed a targeted screen and discovered that RNAi-mediated knock down of 5HT2A in R4d neurons abrogated the lifespan effects caused by death perception. We also discovered that FOXO expression, a transcription factor associated with the insulin-signaling pathway and a known regulator of aging, was required in R4d neurons. Further evidence suggests a role for the insulin pathway in mediating the effects of death perception on lifespan; dilp3 and dIlp5, but not dIlp2, showed increased mRNA levels in dead-exposed wild type flies compared to the unexposed control animals. In addition, this mRNA increase was reflected at the protein level as dIlp3 immunostaining was higher in dIlp-expressing neurons of dead exposed compared to the unexposed controls. At present we are testing a model in which visual input to the ellipsoid body influences insulin production to modulate psychological state, physical health, and aging.

The Neuronal and Molecular Mechanisms by Which Death Perception Impacts Fly Behavior and Lifespan