Testing effects of nutrients on the brain and behavior
The purpose of this project is to better understand how activity in the brain helps animals to obtain the correct nutrients from their world. Of particular interest is protein which all animals, including humans, need to stay alive. Protein is made up of amino acids and many cannot be synthesized by the body meaning there are serious health consequences if they are not found in the diet. Many species are known to control protein intake but how the brain is involved is almost completely unknown. In addition, it has been proposed that low dietary protein alters appetite in humans to cause obesity.
In this project, rats and mice will be kept on diets differing in protein level and intake of various nutrients will be measured. Activity in the brain will be assessed using three techniques – electrophysiology, fiber photometry, and two photon imaging. For all three of these techniques, rodents will undergo a surgical operation under general anesthesia in which a recording device is inserted into the brain. When they recover, brain activity can be measured while they are awake and drinking solutions containing different nutrients. In some experiments, a tube will also be implanted to let nutrients be placed directly in the stomach.
The expected benefit is that important information on how the brain responds to nutrients will be gained. There are health challenges linked to eating too much food, not eating enough food, or eating the wrong type of foods. Obesity is one example but diabetes, heart disease and malnutrition are other associated examples. Although the research in this project is basic science it will inform the way we think about these diseases and will potentially lead to positive ideas for treatment.
The project will use a maximum of 96 rats and 1944 mice. Some of these mice will be genetically-modified mice that will allow a certain type of brain cell to be targeted for recording or activation. Out of the 2040 animals, the severity levels will be: sub-threshold=8%, mild=31%, and moderate=61%.
The 3Rs will be adhered to in numerous ways. First, there will be a reduction in the number of animals used by careful statistical design. In particular, we use a form of statistical analysis that allows us to stop an experiment early if there is no effect thereby reducing the number of unnecessary animals. Also, wherever possible we use techniques that allow us to record many cells from the same animal, again, reducing the number of animals required. Second, we use refined methods throughout including providing environmental enrichment in all cages, housing animals in groups rather than on their own, and handling rodents in a sensitive manner. Third, replacement of these studies by non-animal studies is difficult as it is impossible to study the connections between the brain and the stomach in an in vitro model or in a computer. However, we have conducted some recent experiments in an invertebrate, the pond snail, in an attempt to develop new knowledge using less sentient animals.
In this project, rats and mice will be kept on diets differing in protein level and intake of various nutrients will be measured. Activity in the brain will be assessed using three techniques – electrophysiology, fiber photometry, and two photon imaging. For all three of these techniques, rodents will undergo a surgical operation under general anesthesia in which a recording device is inserted into the brain. When they recover, brain activity can be measured while they are awake and drinking solutions containing different nutrients. In some experiments, a tube will also be implanted to let nutrients be placed directly in the stomach.
The expected benefit is that important information on how the brain responds to nutrients will be gained. There are health challenges linked to eating too much food, not eating enough food, or eating the wrong type of foods. Obesity is one example but diabetes, heart disease and malnutrition are other associated examples. Although the research in this project is basic science it will inform the way we think about these diseases and will potentially lead to positive ideas for treatment.
The project will use a maximum of 96 rats and 1944 mice. Some of these mice will be genetically-modified mice that will allow a certain type of brain cell to be targeted for recording or activation. Out of the 2040 animals, the severity levels will be: sub-threshold=8%, mild=31%, and moderate=61%.
The 3Rs will be adhered to in numerous ways. First, there will be a reduction in the number of animals used by careful statistical design. In particular, we use a form of statistical analysis that allows us to stop an experiment early if there is no effect thereby reducing the number of unnecessary animals. Also, wherever possible we use techniques that allow us to record many cells from the same animal, again, reducing the number of animals required. Second, we use refined methods throughout including providing environmental enrichment in all cages, housing animals in groups rather than on their own, and handling rodents in a sensitive manner. Third, replacement of these studies by non-animal studies is difficult as it is impossible to study the connections between the brain and the stomach in an in vitro model or in a computer. However, we have conducted some recent experiments in an invertebrate, the pond snail, in an attempt to develop new knowledge using less sentient animals.