Hungry, stressed chicks? Understanding Hypothalamic Regulation of Appetite in Birds

生命早期是生命中极其重要的时期，胚胎发育过程中所经历的压力可能会对一生产生影响。在鸟类中，将孵化中的母亲或发育中的蛋暴露在压力刺激下会改变其存活率、繁殖成功率、生产力、后代的健康和福利。食欲和体重是由神经系统和内分泌系统密切调节的，而这些系统特别容易受到压力的影响。在这个项目中，我们将研究早期生活应激编程对大脑喂养回路的神经生物学机制。目的是确定鸟类的食欲是如何形成的，以及它是如何受到产前压力的影响的。鸟类大脑中的进食回路在胚胎发育的后半期建立，在孵化前1 - 2天达到其特征。尽管鸟类神经回路形成的发育在很大程度上是不确定的，但某些物种的大脑发育在孵化前就基本完成了，比如鹌鹑，它们的幼鸟相对成熟，从孵化开始就能活动。由于这些神经回路似乎发育迅速，在孵化后需要发挥功能，我们假设大脑喂养回路在发育过程中特别容易受到应激激素的影响。在这里，我们将研究这是否会导致脑回路功能的永久性失调，从而导致孵化后特征的变化。我们将研究鸟类早期大脑回路积极发育和形成连接时大脑功能活动和行为的变化。我们还将研究早期生活压力下的胚胎和小鸡是否在喂养回路上存在差异，因为我们从之前的工作中得知，它们成年后体重较轻。我们将通过将皮质酮注射到受精卵中，将应激激素（皮质酮）的水平提高到自然产生的高水平。这模仿了压力母亲将压力激素信号沉积到蛋中（鹌鹑早期生活压力编程模型）。我们所有的研究都将在雄性和雌性鹌鹑中进行，因为有证据表明在食欲调节方面存在性别差异。我们将通过使用神经元激活标记来绘制正常鸟类大脑和随后暴露于产前皮质酮的大脑中的功能性喂养（饥饿和饱足）途径。我们将确定细胞是增加还是减少食欲。我们还将调查早期生活压力是否会影响雏鸟的摄食行为和雏鸟孵化后的一般运动。我们将通过量化基因表达来检验在胚胎和雏鸡经历了早期生活压力编程后，调节食欲的关键激素和神经回路是否发生了变化。我们将使用一种被称为电生理学的技术来记录大脑进食回路的电脉冲，研究早期生活压力是否会改变进食回路中细胞对葡萄糖的敏感性。检测到葡萄糖变化的脑细胞将身体的代谢需求告知大脑。有趣的是，在鸟类脑液中测量到的葡萄糖水平是哺乳动物的几倍，这表明葡萄糖调节在鸟类中可能更重要。我们已经为鹌鹑胚胎和小鸡开发了一种新的大脑切片准备，并且（据我们所知）是英国目前唯一能够做到这一点的实验室。我们将提供关于鸟类大脑对葡萄糖敏感性的新数据，并量化细胞性质和行为是否有变化。这些研究很重要，因为它们将为新孵化的小鸡调节食欲的大脑机制提供独特的信息，并阐明早期生活压力可能会影响大脑喂养回路的机制。

Early life is extremely important time of life and stress experienced as a developing embryo can have lifelong consequences. In birds, exposing an incubating mother or developing egg to stressful stimuli can change survival, breeding success, productivity, health and welfare of the offspring. Appetite and body weight are closely regulated by the nervous and endocrine systems and these systems are particularly vulnerable to stress. In this project we will investigate the neurobiological mechanisms of early life stress programming on brain feeding circuits. The aim is to determine how appetite is developed in birds and how it is affected by pre-natal stress.Feeding circuits in the bird brain are established during the second half of embryonic development and they achieve their characteristics 1 to 2 days before hatch. Although the development of the neural circuit formation is largely undetermined in birds, brain growth is largely complete before hatching in species, such as quail, where the young are relatively mature and mobile from hatch. As these neural circuits appear to develop rapidly and need to become functional after hatch, we hypothesise that brain feeding circuits are especially vulnerable to stress hormones during development. Here we will investigate whether this results in permanent dysregulation of brain circuit function leading to changes in post hatch characteristics. We will investigate the changes in functional brain activity and behaviour across early life when avian brain circuits are actively developing and forming connections. We will also examine whether embryos and chicks exposed to early life stress have differences in their feeding circuits as we know from our previous work that they have lower body weights as adults. We will increase levels of stress hormone (corticosterone) to naturally occurring high levels by injecting corticosterone into fertilised quail eggs. This mimics the stress hormone signal that stressed mothers deposit into the egg (quail early life stress programming model). All our studies will be performed in both male and female quail as there is evidence to suggest there are sex differences in appetite regulation.1. We will map the functional feeding (hunger and satiation), pathways within the normal bird brain and subsequently in brains exposed to prenatal corticosterone by using a marker of neuronal activation. We will identify whether the cells increase or decrease appetite. We will also investigate whether early life stress affects feeding behaviour and the general movement of the chicks once they have hatched.2. We will examine whether the key hormone and neural circuits, that regulate appetite, are changed in embryos and chicks that have been subjected to early life stress programming by quantifying the gene expression.3. Using a technique to record electrical impulses of the feeding circuits in the brain called electrophysiology, we will investigate whether early life stress changes the sensitivity of cells in the feeding circuit to glucose. Brain cells that detect changes in glucose inform the brain of the metabolic needs of the body. Interestingly, the glucose levels measured in brain fluid of birds are several fold higher than in mammals indicating that glucose regulation may be more important in birds. We have developed a novel brain slice preparation for quail embryo and chick and are (to our knowledge) the only lab in the UK currently able to do this. We will provide novel data on the sensitivity of the bird brain to glucose and quantify if there are changes in the cells properties and actions.These studies are important as they will provide unique information into the brain mechanisms that regulate appetite in newly hatched chicks and elucidate the mechanisms by which early life stress may program the feeding circuits in the brain.