The neural circuits underlying gustatory perception in flies

动物使用味觉来决定潜在的食物;具有高营养价值的物质 有价值的食物被摄入，而毒素和有害物质被拒绝。有趣的是，这些行为 在很多物种中都很常见苍蝇对甜味剂和苦味剂的反应有不同的刻板行为： 甜味物质，通常富含热量，是食欲和接受，而苦味化合物，通常是有害的， 拒绝和回避。刺激质量和行为反应之间的联系表明， 苦味物质在大脑中的表现不同。老鼠处理关于甜和苦的信息 物质通过标记线平行。相比之下，在蛾类中， 描述了单个的味素，表明神经回路是收敛的。目前未知 这些不同的模型中的哪一个在苍蝇中起作用。要解决这个问题，就需要全面 逐层分析味觉回路。虽然我们对一阶苦内层次的理解 而甜味回路是相当先进的，对味觉神经元的二级水平知之甚少。 系统到目前为止，大多数已被表征的二级神经元都是通过以下方法确定的： 基因筛查由于一阶味觉投射的分布性质，人们不能识别 二级神经元的树突的位置，因为已经成功地在嗅觉回路。 此外，果蝇在身体的各个部位都有味觉神经元，我们假设， 味觉地图存在于大脑中。所有这些重要的知识缺口都将受益于一个强大的遗传学 用于神经回路的跨突触标记的系统。 我们最近发展了一种新的跨突触追踪和操纵神经回路的方法 称为trans-Tango。我们已经在果蝇的嗅觉系统中验证了trans-Tango，并在 处理有关甜味化合物信息的味觉回路。我们的分析显示，第二- 甜味回路中的顺序神经元投射到大脑中的神经调节区域，其中一些已知 参与控制进食行为。在这里，我们建议实现trans-Tango来识别第二个- 在苦涩的电路中安排投影。我们的初步数据表明， 苦回路与二阶甜投射非常相似。我们提出了一个多管齐下的战略， 包括解剖学，功能和行为分析，旨在详细描述第二和第三个， 在甜和苦回路中的顺序投射。为了我们的分析，我们将建立新版本的trans- Tango通过钙成像和光遗传学结合了新的电路功能分析模块， 用于交叉连接性研究，以及用于交叉投影分析。因此，我们的研究将加深我们的 了解果蝇的味觉信息处理，这是一个对人类健康非常重要的课题， 味觉与昆虫作为许多昆虫传播疾病的主要媒介的作用的相关性。

Animals use the sense of taste to make decisions regarding potential food; substances with high nutritional value are ingested, while toxins and harmful substances are rejected. Interestingly, these behaviors are common across many species. Flies respond to sweet and bitter tastants with different stereotyped behaviors: sweet substances, often calorie rich, are appetitive and accepted, while bitter compounds, usually harmful, are rejected and avoided. The linkage between stimulus quality and behavioral response suggests that sweet and bitter tastants are represented differently in the brain. Mice process information regarding sweet and bitter substances in parallel through labeled lines. By contrast, in moths, a distributed combinatorial code for individual tastants was described, suggesting that the neural circuits are convergent. It is currently unknown which of these distinct models is operative in flies. Addressing this question will require a comprehensive analysis of the gustatory circuits layer by layer. While our understanding of the first-order level within the bitter and sweet circuits is rather advanced, little is known about neurons in the second-order level of the gustatory system. Most of the second-order neurons that have been characterized thus far have been identified by genetic screens. Due to the distributive nature of the first-order gustatory projections, one cannot identify the second-order neurons by the location of their dendrites, as has been done successfully in the olfactory circuits. In addition, flies have gustatory neurons in various parts of their body, and we hypothesize that a somatotopic gustatory map exists in the brain. All of these important gaps of knowledge would benefit from a robust genetic system for transsynaptic labeling of neural circuits. We have recently developed a new method for transsynaptic tracing and manipulation of neural circuits termed trans-Tango. We have validated trans-Tango in the olfactory system of flies and established it in the gustatory circuits that process information regarding sweet compounds. Our analysis revealed that second- order neurons in the sweet circuits project to neuromodulatory areas in the brain, some of which are known to be involved in controlling feeding behavior. Here we propose to implement trans-Tango to identify second- order projections in the bitter circuits. Our preliminary data suggest that the second-order projections in the bitter circuits are very similar to the second-order sweet projections. We propose a multipronged strategy that involves anatomical, functional and behavioral analyses aimed at characterizing in detail the second- and third- order projections within the sweet and bitter circuits. For our analysis, we will establish new versions of trans- Tango that incorporate new modules for functional analysis of circuits via calcium imaging and optogenetics, for intersectional connectivity studies, and for multicolor projection analysis. Thus, our studies will deepen our understanding of gustatory information processing in flies, a topic of high importance for human health in view of the relevance of the sense of taste for the role of insects as major vectors of many insect-born diseases.