Solving conflicts: Modulation of choices and actions in the fly.

解决冲突：即时调整选择和行动。

• 批准号: BB/W016249/1
• 负责人: Carolina Rezaval
• 金额: $ 70.03万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW016249%2F1
• 关键词: Solving; conflicts; Modulation; choices; actions

Effective action-selection involves evaluating information from the outside world and our intrinsic needs to select the most appropriate action for each situation. Yet little is known about how external and internal cues are weighed and integrated in the brain to prioritise actions.This project investigates this fundamental biological problem using the fruit fly Drosophila, an excellent system to investigate the mechanistic basis of behaviour. We will build on our recent knowledge of the key neurons that mediate the choice between feeding and mating (Cheriyamkunnel et. al., Curr.Biol 2021) to characterise the mechanism that integrates modulatory signals to prioritise actions.Fruit flies have a brain of only 100,000 neurons, most of which have been mapped. Thanks to new genetic tools, single neurons can be manipulated and recorded in Drosophila with a level of temporal, spatial and genetic precision that is not available in any other model organism. With these tools, we can study how cues from the environment and from inside the animal are evaluated in brain circuits to select appropriate actions.The choice between food or sex is a pretty fundamental one - we have to eat to live and we have to reproduce to pass on our genes to the next generation. We have recently created an assay where food- and sex-deprived flies are confronted with the decision of whether to prioritise feeding or mating. These behaviours cannot be simultaneously displayed in flies, forcing the animal to make a decision and prioritise what to do. Crucially, we know a great deal about the neural basis of courtship and feeding behaviours. Thus, this assay is well suited to identify fundamental principles of action-selection that might apply to other behavioural conflicts and the brains of other organisms.We discovered that if a male fly is very hungry and sexually aroused, he will choose to eat over courting a female. However, the choice also depends on other factors like the quality of the food on offer and on how hungry and sex deprived the animal is. We found that the neurons that tell the fly to go and eat, or to go and mate are essentially competing with each other. If the need to eat is most urgent, the feeding neurons will take over; if the threat of starvation is less, then the urge to reproduce will win. Further, we found that the presence of a female makes the males eat faster, allowing them to move on to sex very quickly. These findings suggest that conflicting states (e.g. the urge to eat and to reproduce) do not always inhibit each other but may help each other. Our work provides the unique opportunity to understand how flies integrate sensory cues to make these behavioural choices, and ask what it reveals about the way the brain functions. In this project, we will identify the signals that convey hunger state, as well as the cues that broadcast the presence of a potential mate, to the action-selection centre in the brain. We will study how these signals are integrated in the neurons that steer the animal's actions, making each option more or less attractive. In objective 1, we will define how hunger signals are integrated in the brain to promote feeding over courtship. In objective 2, we will study how the motivation to mate makes the male eat faster, allowing him to quickly move to the female. In objective 3, we will reveal how males determine when to stop a given behaviour (e.g., feeding) to engage in another important task (e.g., mating). This action-selection is an example of the everyday conflicts animals need to solve but are difficult to tackle in mammals. By studying how the brain makes decisions at a molecular, cellular and circuit level, in a simpler system, we aim to reveal fundamental principles of action-selection that might be common to many species. This knowledge, in turn, will provide insight into how other more complex brains work, like our own.

有效的行动选择涉及评估来自外部世界的信息和我们的内在需求，以针对每种情况选择最合适的行动。然而，人们对外部和内部线索如何权衡并整合到大脑中以确定行动的优先顺序知之甚少。该项目利用果蝇研究这一基本生物学问题，果蝇是研究行为机制基础的优秀系统。我们将基于我们最近对介导进食和交配之间选择的关键神经元的了解（Cheriyamkunnel 等人，Curr.Biol 2021）来描述整合调节信号以优先考虑行动的机制。果蝇的大脑只有100,000 个神经元，其中大部分已被映射。借助新的遗传工具，可以在果蝇中操纵和记录单个神经元，其时间、空间和遗传精度水平是任何其他模型生物所不具备的。借助这些工具，我们可以研究如何在大脑回路中评估来自环境和动物内部的线索，以选择适当的行动。食物或性之间的选择是一个非常基本的选择 - 我们必须吃饭才能生存，我们必须繁殖将我们的基因传递给下一代。我们最近创建了一种检测方法，让食物和性被剥夺的果蝇面临是否优先进食或交配的决定。这些行为不能同时在果蝇身上表现出来，迫使动物做出决定并确定要做什么的优先顺序。至关重要的是，我们对求偶和进食行为的神经基础了解很多。因此，这种测定非常适合确定可能适用于其他行为冲突和其他生物体大脑的行动选择的基本原理。我们发现，如果雄性果蝇非常饥饿并且性唤起，他会选择吃东西而不是求爱一名女性。然而，选择还取决于其他因素，例如所提供食物的质量以及动物的饥饿程度和性剥夺程度。我们发现，告诉果蝇去吃东西或去交配的神经元本质上是在相互竞争。如果最迫切需要吃东西，喂养神经元就会接管；如果饥饿的威胁较小，那么繁殖的冲动就会获胜。此外，我们发现雌性的存在会使雄性吃得更快，从而使它们能够很快进行性行为。这些发现表明，冲突的状态（例如进食和繁殖的冲动）并不总是相互抑制，而是可能相互帮助。我们的工作提供了独特的机会来了解果蝇如何整合感官线索来做出这些行为选择，并探究它揭示了大脑功能的方式。在这个项目中，我们将识别传达饥饿状态的信号，以及向大脑中的行动选择中心广播潜在伴侣存在的线索。我们将研究这些信号如何整合到引导动物行为的神经元中，从而使每种选择或多或少具有吸引力。在目标 1 中，我们将定义饥饿信号如何整合到大脑中以促进进食而不是求偶。在目标 2 中，我们将研究交配动机如何使雄性吃得更快，从而使其能够快速转向雌性。在目标 3 中，我们将揭示雄性如何确定何时停止特定行为（例如进食）以从事另一项重要任务（例如交配）。这种行动选择是动物需要解决的日常冲突的一个例子，但在哺乳动物中却很难解决。通过研究大脑如何在更简单的系统中在分子、细胞和电路水平上做出决策，我们的目标是揭示许多物种可能共有的行动选择的基本原理。反过来，这些知识将让我们深入了解其他更复杂的大脑（比如我们自己的大脑）是如何工作的。

项目成果

Measurement of Drosophila Reproductive Behaviors

果蝇生殖行为的测量

• DOI: http://dx.10.1101/pdb.top107866
• 发表时间: 2023
• 期刊: Cold Spring Harbor Protocols
• 作者: Von Philipsborn A

Female Fly Postmating Behaviors.

雌蝇交配后行为。

• DOI: http://dx.10.1101/pdb.prot108108
• 发表时间: 2023
• 期刊: Cold Spring Harbor protocols
• 作者: Von Philipsborn AC

Single-Pair Courtship and Competition Assays in Drosophila

果蝇的单对求爱和竞争测定

• DOI: http://dx.10.1101/pdb.prot108105
• 发表时间: 2023
• 期刊: Cold Spring Harbor Protocols
• 作者: Von Philipsborn A

Courtship Conditioning/Suppression Assays in Drosophila.

果蝇的求爱条件/抑制测定。

• DOI: http://dx.10.1101/pdb.prot108106
• 发表时间: 2023
• 期刊: Cold Spring Harbor protocols
• 作者: Von Philipsborn AC

Probing Acoustic Communication during Fly Reproductive Behaviors

探讨苍蝇繁殖行为期间的声音交流

• DOI: http://dx.10.1101/pdb.prot108107
• 发表时间: 2023
• 期刊: Cold Spring Harbor Protocols
• 作者: Von Philipsborn A