The brainstem signals dual motivational valence following ingestion

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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.