The Role of Nucleus Tractus Solitarii (nTS) Neurons in Cardiorespiratory Dysfunction Associated with Alzheimer's Disease

Alzheimer's disease (AD) is associated with dysfunction of cardiorespiratory control. The mechanisms behind these alterations are not understood. The nTS is critical in cardiorespiratory homeostasis and reflex function, and may play a crucial role in AD dysautonomia. Here we examined autonomic and respiratory regulation, and neuronal alterations in the nTS of an established rodent AD model (CNS Streptozotocin (STZ)‐induced). Results are compared to saline‐injected control rats. In vivo plethysmography revealed a strong trend for blunted hypoxia/chemoreflex‐induced increases in breathing ( p =0.068). Furthermore, baroreflex‐mediated sympathoexcitation to hypotension was markedly blunted in AD rats ( p 蠄0.01), consistent with orthostatic hypotension observed in AD patients. To examine the neuronal alterations in the nTS, patch clamp recordings were made in in vitro slices. When compared to control, AD rats show significantly increased network activity ( p 蠄0.01), spontaneous spike discharge and enhanced discharge to current injection (~40% increase vs. control; p 蠄0.001). Our results suggest increased basal excitation of the nTS neuronal network and blunted cardiorespiratory reflex responses, which may play an important role in the autonomic and respiratory dysfunction observed in AD patients. Supported by: RO1 HL098602, AHA 12POST11670002