The genetic and neural basis of female behaviours in Drosophila.

确定复杂行为变异的潜在遗传和神经基础仍然是行为生物学的主要目标和挑战。这项拟议的研究计划确定了复杂行为中的单个遗传变化、单个神经元和潜在的神经回路。我们使用果蝇模型系统中可用的强大遗传工具，专注于女性配偶拒绝行为和女性攻击性的鲜为人知但却至关重要的特征。交配行为和攻击性的特征已经在雄性的遗传和神经水平上得到了广泛的研究，但对雌性的了解很少。由于雌性选择往往是是否发生交配的决定性因素，包括防止近亲物种之间的交配，而雌性的攻击性对资源获取和繁殖可能是重要的，因此基础自然科学知识的这种差距限制了我们就关键行为途径的进化以及这些途径对物种形成的影响建立更大规模进化理论的能力。这一差距也阻碍了对男性和女性复杂生殖行为的形成是否存在分歧或凝聚力的探索。为了纠正这一差距：(1)我们将使用有针对性的遗传变化来确定导致女性接受能力变异的特定遗传多态，重点放在我们之前发现的影响物种特定雌性配偶拒绝行为变异的两个基因上。(2)我们将通过在候选神经元的亚群中定位转录基因敲除来确定这两个候选基因通过哪些神经元影响女性排斥反应。(3)我们将使用尖端工具来识别我们最近发现的一条女性排斥通路的上游和下游回路，该通路涉及一对章鱼胺神经元，当神经元沉默时，该神经元会诱导主动的雌性排斥反应。(4)我们将使用一系列果蝇工具来识别雌性特有攻击性的神经递质和回路，重点放在我们最近发现的一小群神经元上，这些神经元在过度激活时诱导雌性特有的攻击性；这些神经元在雄性中诱导求偶。这四个目标的完成将首次确定负责隔离物种的雌性行为的基因，首次确定影响物种隔离的神经元，首次精细描述中枢神经系统中雌性拒绝配偶行为的神经元和回路，以及首次表征雌性特有的攻击行为的神经元和回路。如果我们要全面了解复杂行为是如何产生的，了解这些关键女性特有行为的遗传和神经基础是至关重要的。

Identifying the underlying genetic and neural basis of variation in complex behaviour remains a primary goal, and challenge, in behavioral biology. The proposed research program identifies single genetic changes, individual neurons, and the neural circuitry underlying variation in complex behavior. We focus on the poorly-understood, yet critical, traits of female mate rejection behaviour and female aggression, using the powerful genetic tools available within the Drosophila model system. The traits of mating behavior and aggression have been extensively studied at the genetic and neural level in males, but are poorly understood in females. Since female choice is more often the deciding factor in whether mating occurs, including preventing matings between closely-related species, and female aggression can be important for resource acquisition and reproduction, this gap in fundamental natural sciences knowledge limits our ability to make larger-scale evolutionary theories about the evolution of critical behavioural pathways and the effect of those pathways on speciation. This gap also prevents an exploration of whether there is divergence or cohesiveness in the formation of complex reproductive behaviours in males and females. To rectify this gap: (1) We will use targeted genetic changes to determine the specific genetic polymorphisms that underlie variation in female receptivity, focusing on two genes we previously identified as affecting variation in species-specific female mate rejection behavior. (2) We will identify the neurons that these two candidate genes are acting through to affect female rejection by targeting transcript knockdown in subsets of candidate neurons. (3) We will use cutting-edge tools to identify the upstream and downstream circuitry of a female rejection pathway we recently identified involving a single pair of octopamine neurons that induce active female rejection when the neurons are silenced. (4) We will use an array of Drosophila tools to identify the neurotransmitters and circuitry of female-specific aggression, focusing on a small cluster of neurons we recently identified that induce female-specific aggression when these neurons are hyper-activated; these same neurons induce courtship in males. Completion of these four objectives will provide the first characterization of a gene for female behaviours responsible for isolating species, the first identification of neurons affecting species isolation, the first fine-scale characterization of neurons and circuitry in the central nervous system for female mate rejection behavior, and the first characterization of neurons and circuitry for female-specific aggression. Understanding the genetic and neural basis of these key female-specific behaviours is essential if we are to have a complete perspective of how complex behaviours are generated.