Grant: Project Grant

Sleep plays an important role in the formation of memories. Losing sleep, even for a few hours, can have an unfavourable effect on remembering. Intriguingly, comorbidities of sleep disturbances and cognitive decline have been associated with many neurological disorders and ageing. In our previous studies, we found that patients with Christianson syndrome, a complex brain disorder, often experience sleep disturbances. Interestingly, those with more severe sleep issues tend to have more behavioral and emotional problems during the day. Christianson syndrome is caused by loss-of-function mutations in a gene encoding a specific protein known as NHE6, crucial for the maintenance of the balance of acidity in certain cell parts. NHE6 is vital for proper function of neurons and the brain. The hippocampus, a critical area in the brain, plays a key role in forming memories. When we sleep, the hippocampus replays previously formed patterns of neuronal activity, and this phenomenon is crucial for memory formation. As NHE6 is highest expressed in the cell type that orchestrates hippocampal replay, Dr McKinney (expertise on Christianson syndrome, cellular molecular mechanism of neuronal circuitry) and Dr Peyrache (expertise in sleep and systems neurosciences on spatial cognition and memory formation) bring together their expertise to explore new frontiers in understanding how sleep affects memory in neurological disorders. In this grant, we build on our previous published work and extensive preliminary data to study how the lack of NHE6 leads to disturbances in neuronal activity and memory. We have developed novel tools and assembled a multidisciplinary team that places us in a unique position to make ground-breaking discoveries in how NHE6 contributes to sleep and memory. Our research promises to not only advance our understanding of Christianson syndrome but also pave the way for new treatments that could improve the lives of those affected by similar neurological conditions.