TP3 - Infection and behavior: The role of the mushroom body, AMPs and octopamine in brain-body communication

适应行为以避免受污染或危险食物的能力在物种中高度保守，无论它们的首选食物来源，寿命或解剖结构如何。尽管这种类型的行为适应很普遍，但动物如何将消化系统中有毒或致病物质的存在与指导进食和食物选择的神经回路联系起来仍然不完全清楚。在第一个资助期内，我们在果蝇中提供了证据，证明病原体摄入是通过神经调节（即章鱼胺能）神经元中的免疫受体PGRP-LC和-LE被神经系统识别的。此外，基于我们的数据牵连的嗅觉和昆虫的学习和记忆中心，蘑菇体（MB），我们提出了一个模型，其中病原体摄入检测到免疫受体的章鱼胺能神经元，反过来将此信息传递给MB，在那里它持久地调节喂养行为可能通过类似于短期嗅觉联想学习的机制。在这一点上，我们希望在第二个供资期间解决的几个问题仍然没有答案。我们期望，这个后续项目将阐明章鱼胺信号的作用和起源，以及PGRP/Imd信号在这些神经元中的功能，在MB依赖性获得性食物厌恶。此外，我们希望阐明抗菌肽（AMP）的作用，以及它们是否与神经肽类似或一致。最后，我们将描述病原体摄入对MB及其他神经元的状态和可塑性的影响。总之，这个项目的结果将有助于澄清学习中心在学习避免危险食物来源的重要能力中的作用。

The ability to adapt behavior to avoid contaminated or dangerous food is highly conserved across species, regardless of their preferred food source, life span or anatomy. Despite the prevalence of this type of behavioral adaptation, how animals make the connection between the presence of toxic or pathogenic substances in their digestive system and the neural circuits that guide feeding and food choice remains incompletely understood. During the first funding period, we have provided evidence in Drosophila melanogaster that pathogen ingestion is recognized by the nervous system through the immune receptors PGRP-LC and -LE in neuromodulatory (i.e. octopaminergic) neurons. Based in addition on our data implicating the sense of smell and the insect’s learning and memory center, the mushroom body (MB), we propose a model wherein pathogen ingestion is detected by immune receptors in octopaminergic neurons that in turn convey this information to the MB, where it lastingly modulates feeding behavior potentially through mechanisms analogous to short-term olfactory associative learning. At this point, several questions remain unanswered that we wish to address during a second funding period. We anticipate that this follow-up project will clarify the role and origin of octopamine signaling and the function of PGRP/Imd signaling in these neurons in MB-dependent acquired food aversion. Moreover, we hope to shed light on the role of antimicrobial peptides (AMPs) and whether they act similarly as or in concert with neuropeptides. Finally, we will characterize the impact of pathogen ingestion on the state and plasticity of neurons of the MB and beyond. Together, results from this project will help to clarify the role of a learning center in the important ability to learn to avoid dangerous food sources.