Hemalaxmi Karlapudi

Primary cilia are microtubule based organelles, which have been heavily implicated in signalling and hormonal modulation. They have been found to have neuromodulatory receptors localized on them, one of them being Melanin-concentrating hormone receptor 1 (MCHR1). MCH is involved in the regulation of homeostatic processes4, and is also known to stimulate feeding. Furthermore, Ift88 is a protein necessary for proper assembly and functioning of primary cilium. I will be injecting the hippocampus of IFT88fl/fl/IFT88+/flox mice with an AAV virus in order to express Cre. This will allow for the wipeout of primary cilia within that specific region, which will include the MCHR1 receptors. Through this, we hope to find that the mice will have memory loss, due to primary cilia knockout in the hippocampus, a region heavily implicated in long-term memory and memory storage, as well as dysregulation in feeding behaviors due to the MCHR1 KO. To test this, I will be using two behavioral tests: one will be a maze, to test the navigational memory of the mice, and the other will be a food chamber that will be presented to the mice daily, in order to test post-meal consumption. This process will be repeated for 4 weeks, before and after treatment. The progress will be measured over time. To physiologically examine the status of the brain after treatment, and connect it to the results from each mice, the mice will all be perfused in order to extract their brains, and the brains will be cyrosectioned, stained using immunohistochemistry, and imaged using fluorescence microscopy. The aim will be to look for cilia counts before and after treatment, as well as the presence/expression of MCH within the brain. These results will be connected back to how the mice performed behaviorally. A one-way ANOVA will be used to statistically analyze the results.