Neurocognitive Consequences of Intermittent Hypoxia

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Abstract Sleep apnea is a respiratory disorder that causes intermittent hypoxia (IH) and is known to negatively impact learning and memory. Neurobiological processes within the hippocampus appear to be particularly susceptible to IH. Recent work has shown that IH-dependent hypoxia inducible factor 1a (HIF1a) signaling acts in several ways to mediate changes in hippocampal physiology. While HIF1a promotes oxidative stress that disrupts synaptic plasticity and adult neurogenesis, IH-dependent HIF1a signaling also serves to prevent cell loss among neural progenitors. These observations suggest that the outcome of IH-dependent HIF1a signaling is cell-type specific. This project will serve as a mentored research experience of a trainee who is underrepresented in the field of biomedical research. The candidate will test the hypothesis that IH-dependent cell-autonomous HIF1a signaling among VGLUT1 positive and parvalbumin positive cells mediate unique changes to electrophysiological properties in the hippocampus while also causing stage dependent changes to adult neurogenesis. This hypothesis will be tested using a combination of transgenic mouse technologies, electrophysiology, and cell imaging approaches. The knowledge gained from this work will provide mechanistic insights that may inform the development of effective therapies for cognitive decline in sleep apnea while also enhancing trainee diversity within the field of study.