The neural circuits underlying gustatory perception in flies

动物利用味觉来决定潜在的食物；营养丰富的物质 价值被摄取，而毒素和有害物质被拒绝。有趣的是，这些行为 在许多物种中都很常见。苍蝇对甜味和苦味的反应具有不同的刻板印象： 甜味物质，通常富含卡路里，令人胃口大开，容易被人接受，而苦味化合物，通常是有害的。 被拒绝和回避。刺激质量和行为反应之间的联系表明，甜蜜和 苦味在大脑中的表现是不同的。老鼠处理有关甜味和苦味的信息 物质通过标记线平行排列。相比之下，在Moths中，一种分布式组合码 对不同口味的人进行了描述，这表明神经回路是收敛的。目前还不清楚 这些不同的模式中，哪一种在苍蝇身上起作用。解决这个问题将需要一个全面的 对味觉电路进行了逐层分析。而我们对一级水平的理解却在苦涩之中 甜味环路相当先进，对味觉二阶神经元知之甚少 系统。到目前为止，大多数已被表征的二阶神经元已经被鉴定为 基因筛查。由于一阶味觉投影的分布性质，人们不能识别 二阶神经元通过它们树突的位置，就像在嗅觉回路中已经成功地做的那样。 此外，苍蝇身体的不同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差距都将受益于强大的基因 神经回路的跨突触标记系统。 我们最近开发了一种跨突触追踪和操纵神经回路的新方法 名为跨探戈。我们已经在果蝇的嗅觉系统中验证了反式探戈，并在 处理甜味化合物信息的味觉回路。我们的分析显示第二个- 甜味环路中的有序神经元投射到大脑中的神经调节区，其中一些已知 参与控制喂食行为。在这里，我们建议实施TransTango来识别秒- 在苦涩的赛道中进行订单预测。我们的初步数据表明，地球表面的二阶投影 苦味电路与二阶甜蜜预测非常相似。我们提出了一个多管齐下的战略， 涉及解剖学、功能和行为分析，旨在详细描述第二和第三- 在甜蜜和痛苦的循环中进行订单预测。在我们的分析中，我们将建立新版本的TRANS- Tango集成了用于通过钙成像和光遗传学对电路进行功能分析的新模块， 用于相交连通性研究和多色投影分析。因此，我们的研究将深化我们的 了解苍蝇的味觉信息处理，这是一个对人类健康非常重要的话题 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.