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Long-term cognitive decline is common in both adults and children with type 1 diabetes. Recent studies suggest that diabetic ketoacidosis (DKA), a serious complication of poorly controlled diabetes, may contribute to cognitive decline through mechanisms that are poorly understood. In prolonged hypoinsulinemia, DKA occurs because fatty acid breakdown in the liver releases ketones into the bloodstream as fuel for extrahepatic tissues including the brain. The brain is the most energy consuming organ of the body and prefers glucose, but it can also utilize other fuel sources such as lactate and ketone bodies. DKA has been shown to cause both acute and chronic neuroinflammation in the brain. However, it remains unclear how ketone bodies are utilized as metabolic fuels in neurons, and how ketone metabolism may impact synaptic transmission and cognitive function. My lab has been studying the mechanisms of metabolic regulation at the synapse using quantitative optical imaging of single nerve terminals. Our goal is to discover the molecular mechanisms of ketone oxidation and their synaptic effects in the nervous system.