A Sexually-dimorphic Brain Module for Sensory Integration

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？有性繁殖的物种在社会交往中表现出性别差异，表面上是为了提高繁殖成功率和后代的存活率。一组核心的性别典型行为表现，如交配和攻击，虽然可以通过经验来改变，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。动物的生理性别如何指导行为反应？雄性和雌性将感觉输入转化为两性二态行为，这表明这种行为是由不同性别之间的神经回路产生的。先天行为中的两性二态反映了性别分化的神经系统的作用。动物在发育早期就决定了性别，性别决定引发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，从而产生了性别特异性行为。在整个分类群中，这些机制聚集在一起调节两性二态基因的表达，进而指定性别典型的发育和神经回路功能。在果蝇中，性别特异性行为通过两种性别决定转录因子（TFs）——双性（Dsx）和无果性（Fru）——的作用根植于神经系统。我们将注意力集中在表达这些tf的神经元上，以发现神经元群体中解剖学或分子上的性别差异，从而获得一个切入点，进入性别典型行为背后的神经回路，并识别控制成分行为和行为序列的神经元节点。另一种神经回路布线配置被提出产生两性二态行为。神经元只存在于一种性别（性质的差异），可能激活或抑制该性别的两性二态行为。更常见的是，在无脊椎动物和脊椎动物中，一个神经元群体存在于两性中，但在生理、神经元数量或连通性方面表现出性别差异（定量性别差异）。在这种情况下，神经元可能调节显示两性二态行为的概率，或控制两性（功能二价）中不同两性二态行为的显示。我们关注的是表达dsx的神经元的作用。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。我们发现了一组两性二态的dsx神经元，它们对雄性和雌性的感觉整合至关重要。重要的是，我们发现的二态性可以改变雄性和雌性之间的连接和信息流，其中雄性已经进化出专门的视觉通路来处理性别特定的视觉线索，而雌性却没有。我们的目标是了解一般的神经回路，特别是两性二态神经元，是如何产生两性二态行为的，以及分子机制和进化约束是如何塑造这些行为的。

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.