Leveraging the unisexual brain: Investigating the neuronal circuits underlying sexual behaviours.

一个物种的雄性和雌性在求偶期间的复杂相互作用是动物界两性异形行为最显著的例子之一。在确定一个合适的伴侣后，黑腹果蝇雄性会启动一个复杂的求爱仪式，最终以交配告终。雌性果蝇并不主动向雄性求爱，但雌性对雄性求爱的反应决定了它们是否真的会交配。这些都是由大脑控制的复杂决策和行为，但与果蝇一起工作的优势在于使用大量的遗传工具，使我们能够识别和操纵大脑中的相关神经元。有了这些工具，我们可以问大脑在性别之间有什么不同，这些差异如何解释男性和女性对繁殖成功至关重要的不同行为？我们感兴趣的是识别控制求偶行为的神经元，了解它们是如何相互联系的，以及它们是如何协同工作来指定一种性别独有的行为的。特别是，我们专注于理解表达双性（dsx）的神经元的作用，这是果蝇决定性别的关键基因。这些dsx+神经元控制着雄性的求偶行为和雌性的接受能力。然而，人们对大脑中dsx+神经元的具体作用知之甚少，而dsx+神经元被认为是控制交配决定的。我们最近使用遗传工具来操纵女性和男性大脑中这些神经元的功能，并评估其对性行为的影响。出乎意料的是，当我们人工激活雌性大脑中的dsx+神经元时，这些雌性开始表现得像雄性一样，对其他雌性或雄性表现出雄性典型的求爱行为。这个实验表明，无论生理性别如何，男性和女性的大脑都有必要的神经元来诱导男性特有的行为。那么，为什么雌性通常表现得不像雄性呢？男性和女性的大脑有什么不同，让他们以性别合适的方式行事？利用我们的实验诱导雌性的雄性典型求爱行为，我们现在可以研究大脑中的性别差异，这些差异导致只有雄性表现出这些求爱行为。具体来说，我们建议解决以下基本问题：(i)大脑中的哪些特定神经元能够诱导雌性的雄性典型求爱行为？（ii）它们的活动在两性之间有何不同？（iii）我们能否在相同回路的其他神经元中识别出性别差异，从而解释两性二态行为？这项研究为研究神经元如何以不同的方式控制雌性和雄性的交配决定提供了机会。比较两性大脑中神经元的结构、功能和活动将揭示果蝇无性别和性别特异性回路背后的大脑组织原理。这些研究为理解跨物种存在的基本神经元机制提供了巨大的潜力，并代表了理解高等生物复杂的内部工作的关键一步。

The complex interplay between a male and female of a species during courtship is one of the most remarkable examples of sexually dimorphic behaviour in the animal kingdom. Upon identifying a suitable partner, Drosophila melanogaster males initiate an elaborate courtship ritual that culminates with copulation. Drosophila females do not actively court males, yet it is her response to the male's advances that determines whether mating will actually occur. These are complex decisions and behaviours controlled by the brain, but working with flies has the advantage of using a vast array of genetic tools that allows us to identify and manipulate relevant neurons in the brain. With these tools we can ask how does the brain differ between the sexes, and how might these differences explain the distinct behaviours of males and females that are critical for reproductive success? We are interested in identifying neurons that control courtship behaviours, understanding how they are connected with one another, and how they work together to specify a behaviour that is unique to one gender. In particular, we have focused on understanding the role of neurons that express doublesex (dsx), a gene that is key for determining sex in Drosophila. These dsx+ neurons control male courtship behaviour and aspects of female receptivity. Yet little is known about the specific role of dsx+ neurons in the brain, which are believed to control mating decisions. We recently used genetic tools to manipulate the function of these neurons in the brain of females and males and evaluate the effects on sexual behaviour. Unexpectedly, when we artificially activated dsx+ neurons in the female brain, these females began to behave like males by displaying male-typical courtship behaviours towards other females or males.This experiment demonstrates that both male and female brains have the necessary neurons capable of inducing male-specific behaviours, regardless of biological sex. So why don't females normally behave like males? And, what is different about the male and the female brain that allows them to behave in a sex-appropriate manner?Using our assay to induce male-typical courtship behaviours in females we can now study sex differences in the brain that cause only males to exhibit these courtship behaviours. Specifically, we propose to address the following fundamental questions: (i) which specific neurons in the brain are capable of inducing male-typical courtship behaviours in females? (ii) how does their activity differ between sexes? (iii) Can we identify sex-differences in other neurons of the same circuitry that account for sexually dimorphic behaviours? This study provides the opportunity to study how neurons operate differently to control mating decisions in females and males. Comparing the structure, function and activity of neurons in the brain of both sexes will reveal principles of brain organization that underlie unisex and sex-specific circuitry in flies. These studies offer great potential for understanding fundamental neuronal mechanisms that are present across species, and represent a key step toward understanding the complex inner workings of higher organisms.