A pair of dopamine neurons mediate chronic stress signals to induce learning deficit in Drosophila melanogaster

Abstract

Significance Chronic stressful life events could induce learning and memory impairments and increase the risk of developing psychiatric disorders such as depression. Understanding the underlying mechanism is critical for developing effective drugs and treatments. Here, we show that chronic stress induces learning and memory deficits in Drosophila melanogaster. Furthermore, the dopaminergic system is important for regulating susceptibility to chronic stress– induced learning deficit (CSLD). Significantly, a single pair of dopamine neurons, PPL1-γ1pedc neurons, are indispensable for CSLD. We show that PPL1-γ1pedc mediates chronic stress signals to induce abnormal neural activities in mushroom bodies that lead to a learning deficit. Together, these suggest that Drosophila melanogaster can be a powerful model organism for studying the etiology of chronic stress–induced memory impairments. Chronic stress could induce severe cognitive impairments. Despite extensive investigations in mammalian models, the underlying mechanisms remain obscure. Here, we show that chronic stress could induce dramatic learning and memory deficits in Drosophila melanogaster. The chronic stress–induced learning deficit (CSLD) is long lasting and associated with other depression-like behaviors. We demonstrated that excessive dopaminergic activity provokes susceptibility to CSLD. Remarkably, a pair of PPL1-γ1pedc dopaminergic neurons that project to the mushroom body (MB) γ1pedc compartment play a key role in regulating susceptibility to CSLD so that stress-induced PPL1-γ1pedc hyperactivity facilitates the development of CSLD. Consistently, the mushroom body output neurons (MBON) of the γ1pedc compartment, MBON-γ1pedc>α/β neurons, are important for modulating susceptibility to CSLD. Imaging studies showed that dopaminergic activity is necessary to provoke the development of chronic stress–induced maladaptations in the MB network. Together, our data support that PPL1-γ1pedc mediates chronic stress signals to drive allostatic maladaptations in the MB network that lead to CSLD.