The transition from a sexual to a parental brain via nest building

我们提出，筑巢这种鸟类普遍存在的行为，提供了一个独特的窗口来理解物种是如何从性大脑转变为亲代大脑的。在大多数鸟类物种中，繁殖的性阶段的特征是性别间和性别内的行为相互作用，如领土争夺、求偶和保护配偶。其次是确保繁殖成功的亲代行为。一些支持性行为和亲子关系的神经内分泌变化在鸟类中有很好的特征。然而，从性大脑到亲代大脑的快速转变背后的原因尚未得到描述，这就提出了关于在这一关键转变时期物种内部和物种之间观察到的变化的重要基本问题。鸟类的生殖活动是由下丘脑-垂体-性腺（HPG）轴组织的。这个精细调节的系统协调中枢和外围激素的释放，使繁殖只有在环境条件足够好的情况下才能开始。作为对HPG轴刺激的反应，性腺产生性类固醇激素，包括睾酮和17b -雌二醇，它们在调节生殖行为方面起主要作用。鸟类胚胎在发育过程中会受到环境变化的影响，比如每天的温度波动或捕食。为了减轻这些风险，大多数鸟类都在巢中产卵和孵化，并抚养后代。我们之前在斑胸草雀（Taeniopygia guttata）身上发现，在筑巢结束时，循环睾酮水平会发生显著变化，并且在筑巢过程中，性类固醇敏感和不敏感的大脑区域都处于活跃状态。在这里，我们建议确定性类固醇在大脑中的作用，以及关键繁殖阶段转变背后的分子和功能途径。结合尖端技术，我们将描述在求偶、筑巢和早期孵化期间，性类固醇及其专用受体在不同大脑区域的局部变化，并将它们与详细的行为分析联系起来，以更好地理解每种行为/激素关系（目标1）。我们还将通过药理学操作确定性类固醇影响这些行为的主要机制（目标2）。利用下一代测序和先进的生物信息学分析，我们将确定哪些基因在先前确定的已知的性类固醇敏感部位的大脑区域中表现出表达变化（目标3）。最后，在目标4中，我们将使用神经元追踪来描述在筑巢过程中被强烈激活且对性类固醇敏感的大脑区域和神经元网络（目标4）。因此，通过对快速行为转变过程中大脑中性类固醇及其受体的精细变化进行首次全面表征，再加上对它们所支持的分子和细胞网络的详细表征，我们将更好地了解大脑如何支持鸟类从有性阶段向亲代生殖阶段的过渡。

We propose that nest building, a widespread avian behaviour, offers a unique window to understand how species transition from a sexual to a parental brain. In most avian species, the sexual phase of reproduction is characterised by inter- and intra-sex behavioural interactions such as territoriality, courtship and mate guarding. This is followed by parental behaviours that ensure reproductive success. Some neuroendocrine changes that support sexual behaviour and parenthood are well characterised in birds. However, those underlying the rapid transition from a sexual to a parental brain are yet to be described, raising important fundamental questions regarding the variation observed both within and between species on this critical period of transition. Bird reproductive activities are organised by the hypothalamic-pituitary-gonadal (HPG) axis. This finely tuned system orchestrates central and peripheral hormone release enabling breeding to commence only when environmental conditions are good enough for successful offspring rearing. In response to HPG axis stimulation, the gonads produce sex-steroid hormones, including testosterone and 17B-oestradiol, that act centrally to regulate reproductive behaviour. Bird embryos are exposed to environmental changes, such as daily temperature fluctuations or predation during development. To mitigate these risks, most birds build nests into which their eggs are laid and incubated, and the offspring reared.We have previously established in zebra finches, Taeniopygia guttata, that circulating testosterone levels vary significantly towards the end of nest building, and that both sex-steroid sensitive and insensitive brain areas are active during this behaviour. Here we propose to establish where sex steroids act in the brain and the molecular and functional pathway(s) underlying key breeding stage transitions. Combining cutting-edge technologies, we will characterise the local variation(s) of sex steroids and their dedicated receptors in discrete brain areas during courtship, nest building and early incubation, and relate them to detailed behavioural analyses to better understand each of these behaviour/hormone relationships (Objective 1). We will also determine the main mechanisms through which sex steroids influence these behaviours using pharmacological manipulations (Objective 2). Using next generation sequencing and advanced bioinformatic analyses, we will determine which genes show expression changes in previously identified brain regions known to be sites of sex steroid sensitivity (Objective 3). Finally, in Objective 4 we will use neuronal tracing to characterise brain regions and neuronal networks that are strongly activated during nest building and are sex-steroid sensitive (Objective 4). Thus, by performing the first comprehensive characterisation of the fine-scale variations in sex steroids and their receptors in the brain during rapid behavioural transitions, coupled with a detailed characterisation of the molecular and cellular networks they support, we will better understand how the brain supports the transition from sexual to parental reproductive phase in birds.