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

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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.