The neural circuits underlying gustatory perception in flies

果蝇味觉感知的神经回路

• 批准号: 10424479
• 负责人: Gilad Barnea
• 金额: $ 40.42万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10424479
• 关键词: ARNT gene; Address; Agriculture; Anatomy; Animals; Area; Behavior; Behavioral; Body part; Brain; Calcium; Calories; Categories; Cell surface; Chemicals; Code; Data; Decision Making; Dendrites; Desire for food; Disease; Dissection; Drosophila genus; Environment; Feeding behaviors; Food; Genetic; Genetic Screening; Health; Human; Image; Individual; Ingestion; Insecta; Knowledge; Label; Ligands; Light; Location; Malnutrition; Maps; Methods; Modeling; Monitor; Mosaicism; Moths; Mus; Nature; Neurons; Neurosciences Research; Nutritional; Olfactory Pathways; Organ; Other Genetics; Output; Pathway interactions; Peripheral; Process; Proteolysis; Receptor Activation; Reporter; Role; Signal Pathway; Site; Stereotyped Behavior; Stimulus; Synapses; System; Taste Perception; Techniques; Testing; Toxin; behavioral response; combinatorial; design; fly; information processing; neural circuit; neuroregulation; optogenetics; parallel processing; postsynaptic; postsynaptic neurons; receptor; response; sensory system; taste stimuli; taste system; tool; vector

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.

动物利用味觉来决定潜在的食物；高营养物质 价值被摄入，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。果蝇对甜味和苦味促味剂的反应具有不同的刻板行为： 甜味物质通常富含热量，容易引起食欲并被接受，而苦味化合物通常有害，会引起食欲并被接受。 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 促苦味剂在大脑中的表现不同。小鼠处理有关甜味和苦味的信息 通过标记线平行的物质。相比之下，在飞蛾中，分布式组合代码 描述了个体促味剂，表明神经回路是收敛的。目前尚不清楚 这些不同的模型中哪一个在果蝇中起作用。解决这个问题需要全面的 逐层分析味觉回路。而我们对一阶层次的理解却在苦涩之中 甜味回路相当先进，但我们对味觉二阶神经元知之甚少 系统。迄今为止已表征的大多数二阶神经元已被识别 遗传筛查。由于一阶味觉预测的分布性质，人们无法识别 正如在嗅觉回路中成功完成的那样，通过树突的位置来识别二阶神经元。 此外，果蝇身体的各个部位都有味觉神经元，我们假设体位神经元 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遗传基因 神经回路跨突触标记系统。 我们最近开发了一种用于跨突触追踪和神经回路操纵的新方法 称为跨探戈。我们已经在苍蝇的嗅觉系统中验证了反式 Tango，并将其建立在 处理有关甜味化合物的信息的味觉回路。我们的分析表明，第二—— 甜蜜回路中的有序神经元投射到大脑中的神经调节区域，其中一些区域已知 参与控制进食行为。在这里，我们建议实施 trans-Tango 来识别第二个- 痛苦的电路中的秩序预测。我们的初步数据表明，二阶预测 苦味电路与二阶甜味预测非常相似。我们提出了一项多管齐下的战略 涉及解剖学、功能和行为分析，旨在详细描述第二和第三个特征 甜蜜和苦涩循环中的顺序预测。为了我们的分析，我们将建立新版本的反式 Tango 包含通过钙成像和光遗传学对电路进行功能分析的新模块， 用于交叉连通性研究和多色投影分析。因此，我们的学习将加深我们的 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。

项目成果

Complex representation of taste quality by second-order gustatory neurons in Drosophila.

果蝇二阶味觉神经元对味道质量的复杂表征。

• 发表时间: 2022-09-12
• 作者: Snell, Nathaniel J;Fisher, John D;Hartmann, Griffin G;Zolyomi, Bence;Talay, Mustafa;Barnea, Gilad
• 通讯作者: Barnea, Gilad

Transsynaptic mapping of Drosophila mushroom body output neurons.

果蝇蘑菇体输出神经元的突触映射。

• 发表时间: 2021-02-11
• 影响因子: 7.7
• 作者: Scaplen, Kristin M;Talay, Mustafa;Fisher, John D;Cohn, Raphael;Sorkaç, Altar;Aso, Yoshi;Barnea, Gilad;Kaun, Karla R
• 通讯作者: Kaun, Karla R