The brainstem signals dual motivational valence following ingestion

目前，许多英国人都在为体重而苦苦挣扎，这可能会导致糖尿病和心血管疾病等相关问题。除了给个人带来负担之外，治疗肥胖率的上升也给NHS带来了巨大的压力。人们超重的主要原因是他们只是吃得太多了；因此，了解是什么控制了我们的饮食行为是很重要的。如果我们有一段时间没有吃东西，我们就会感到饥饿和不安。这不是一种令人愉快的感觉，因此，我们有动力消费食物。当我们这样做时，饥饿感就消失了，我们可以感到愉悦的饱腹感。当我们不觉得饿的时候，我们把两餐之间的这段时间称为饱腹期。因此，我们可以想象我们的食欲是由相互竞争的感觉控制的：饥饿(一种消极的感觉)和饱足(一种积极的感觉)。或者，当我们经历疾病引起的不同负面感觉时，我们可能会失去食欲，因为我们吃了让我们胃不舒服的东西，或者我们感染了虫子。最后，我们可能会在服用处方药后感到恶心或不适，这可能是为了帮助我们应对糖尿病或癌症。在所有这些情况下，是否进食的决定由我们大脑的两个部分控制。靠近大脑底部的下丘脑从身体的其他部位收集大量信息，包括我们的能量状态(我们刚刚吃了没有)、一天中的时间、我们是否活跃等等。关于我们吃了什么和吃了多少的信息来自肠道到大脑后部的第二部分，即所谓的脑干。脑干收集来自肠道的所有信息，然后将其传递到下丘脑。因此，脑干和下丘脑中的复杂回路，以及大脑的其他部分，控制着我们的饮食行为。我们已经在小鼠的脑干中识别出对来自肠道的不同信号做出反应的细胞(神经元)。例如，一种类型的神经元在老鼠吃过饭时做出反应，而另一种类型的神经元在老鼠吃了让它感觉不舒服的东西时做出反应。我们的实验室有了新的基因“工具”，可以让我们研究这些不同的神经元是如何运作的。例如，我们培育了不同类型的小鼠，允许我们有选择地人工激活这些神经元，并阻止小鼠进食，即使它们非常饥饿。然而，激活这些神经元建立的一些连接，会使小鼠感到满足，而另一些则会让小鼠感到不适。我们认为，这两种类型的神经元分别向大脑的其余部分发出饱腹感和厌恶感的信号。我们将使用我们的工具来绘制大脑中的连接图，展示它们的重要性，并展示在健康和疾病中饮食行为是如何管理的。这些知识将有助于开发控制体重的新药，也有助于治疗副作用较少的糖尿病、癌症和其他疾病的药物。

Currently, many people in the UK struggle with their weight, and this can lead to related problems like diabetes and cardiovascular disease. As well as the burden on individuals, treating the rise in obesity puts immense strain on the NHS. The main reason that people put on excess weight is that they simply over eat; therefore, it is important to understand what controls our eating behaviour. If we have not eaten for a while, we feel hungry and agitated. This is not a very pleasant feeling and, so, we are motivated to consume food. When we do this, the feelings of hunger disappear and we can feel pleasantly full. We call the period in between meals, when we do not feel hungry, satiety. Thus, we can imagine our appetite is controlled by competing feelings: hunger (a negative feeling) and satiety (a positive feeling). Alternatively, we can lose our appetite when we experience different negative feelings, caused by sickness, because we have eaten something that has upset our stomach or if we have caught a bug. Finally, we may feel nauseous or unwell after taking a prescription drug, perhaps to help us cope with diabetes or cancer. In all of these situations, the decision about whether to eat or not is controlled by two parts of our brain. The hypothalamus, near the base of the brain, collects lots of information from the rest of the body about our energy status (have we just eaten or not), the time of day, are we active, etc. Information about what and how much we have eaten comes from the gut to the second part, at the back of the brain, the so-called brainstem. The brainstem collects all the information from the gut and then relays it to the hypothalamus. Thus, complex circuits in the brainstem and hypothalamus, together with other parts of the brain, control our eating behaviour.We have identified cells (neurones) in the brainstem of mice which respond to the different signals coming from the gut. For example, one type of neurone responds when the mouse has eaten a meal, while another responds when the mouse has eaten something which makes it feel unwell. Our laboratories have new genetic "tools" which allow us to investigate how these different neurones function. For example, we have generated different types of mice which allow us to artificially activate these neurones selectively and stop the mice from eating, even if they are very hungry. However, activating some of the connections made by these neurones, cause the mice to feel contented, while others make the mice feel unwell. We believe that these two types of neurone signal satiety and aversion, respectively, to the rest of the brain. We will use our tools to map connections in the brain, demonstrate their importance and show how eating behaviour is managed in both health and disease. This knowledge will help in the development of new drugs to control body weight, but also drugs to treat diabetes, cancer and other diseases, which have fewer side effects.