A Sexually-dimorphic Brain Module for Sensory Integration

一个物种的雄性和雌性在求爱过程中的复杂相互作用是动物界最引人注目的性别二态行为之一。在找到合适的伴侣后，雄性黑腹果蝇就会开始一场精心设计的求偶仪式，最终以交配告终。雌性果蝇不会主动向雄性求爱，但它对雄性求爱的反应决定了交配是否真的会发生。这些都是由大脑控制的复杂决定和行为，但与苍蝇合作的优势在于使用了大量的遗传工具，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，这些差异可能如何解释对生殖成功至关重要的男性和女性的不同行为？有性繁殖物种在社会互动中表现出性别差异，表面上是为了促进繁殖成功和后代的存活。一组核心的性行为表现，如交配和攻击性，虽然可以通过经验改变，但从某种意义上说，它们可以在没有事先训练的情况下表现出来。动物的生物性别如何指导行为反应？男性和女性将感觉输入转化为性二型行为，这表明这种行为是由不同性别的神经回路产生的。这些先天行为中的性二型性反映了性别分化神经系统的活动。动物在发育早期就决定了性别，而性别决定启动了许多不可逆转的性别分化事件，这些事件影响了基因组和环境如何相互作用，从而产生性别特有的行为。在整个类群中，这样的机制汇聚到一起来调节性二态基因的表达，这反过来又指定了性别典型的发育和神经回路功能。在苍蝇中，性别特异的行为通过两个性别决定转录因子(TF)、双性(Dsx)和无果性(Fru)的作用固定在神经系统中。我们将注意力集中在表达这些转录因子的神经元上，以发现神经元群体中的解剖或分子性别差异，以便获得进入典型性别行为的神经回路的入口点，并确定控制组成部分行为和行为序列的神经元节点。已经提出了替代的神经回路布线配置来生成性二态行为。只存在于一种性别中的神经元(质的性别差异)可能激活或抑制该性别的性二态行为。在无脊椎动物和脊椎动物中更常见的是，神经元群体在两性中都存在，但在生理、神经元数量或连接性方面存在性别差异(数量性别差异)。在这种情况下，神经元可能会控制性二型性行为的概率，或者控制两性不同的性二型性行为的显示(功能上的二价体)。我们将重点放在表达dsx的神经元的作用上。这些dsx+神经元控制着雄性求爱行为和雌性接受性的各个方面。然而，人们对dsx+神经元在大脑中的具体作用知之甚少，据信它控制着交配决定。我们确定了一组性别二态的dsx神经元，它们对男性和女性的感觉整合至关重要。重要的是，我们发现的二形性可以改变男性和女性之间的连通性和信息流，其中处理性别特定视觉线索的专用视觉通路在男性身上进化，但在女性身上没有。我们的目标是了解神经回路，特别是性二态神经元，如何产生性二态行为，以及分子机制和进化限制如何塑造这些行为。

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? Sexually reproducing species exhibit sex differences in social interactions, ostensibly to boost reproductive success and survival of progeny. A core set of sex-typical behavioural displays such as mating, and aggression, although modifiable by experience, are innate in the sense that they can be displayed without prior training. How does an animal's biological sex instruct the behavioural response? Males and females transform sensory input into sexually dimorphic behaviours, suggesting that such behaviours are generated by neural circuits that differ between the sexes These sexual dimorphisms in innate behaviour reflect the action of a sexually differentiated nervous system. Animals determine sex early in their development, and sex determination initiates many irreversible sexual differentiation events that influence how the genome and the environment interact to give rise to sex-specific behaviours. Across taxa, such mechanisms converge to regulate sexually dimorphic gene expression that in turn specifies sex-typical development and neural circuit function.In the fly, sex-specific behaviours are hardwired into the nervous system via the actions of two sex determination transcription factors (TFs), Doublesex (Dsx) and Fruitless (Fru). We have focused our attention on neurons that express these TFs to find anatomical or molecular sex differences in neuronal populations in order to gain an entry point into the neural circuits underlying gender-typical behaviours and identify the neuronal nodes that control component behaviours and behavioural sequencing. Alternative neural circuit wiring configurations have been proposed to generate sexually dimorphic behaviours. Neurons present only in one sex (qualitative sex difference) may either activate or inhibit a sexually dimorphic behaviour in that sex. More commonly in invertebrates and vertebrates, a neuronal population is present in both sexes but presents sex differences (quantitative sex difference) in physiology, neuron number, or connectivity. In such cases, the neurons may regulate the probability of displaying a sexually dimorphic behaviour, or control the display of different sexually dimorphic behaviours in the two sexes (functionally bivalent). We have focused on the role of neurons that express dsx. 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 identified a group of sexually-dimorphic dsx neurons that are critical to sensory integration in males and females. Importantly, the dimorphism we uncovered can alter connectivity and information flow between males and females, where a dedicated visual pathway processing sex-specific visual cues has evolved in males, but not females.Our goal is to understand how neural circuits in general, and sexually dimorphic neurons in particular, can generate sexually dimorphic behaviours, and how molecular mechanisms and evolutionary constraints shape these behaviours.