Identification of chemosensitive cells within the lateral hypothalamus

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PROJECT SUMMARY Respiratory chemoreception is the mechanism by which the brain regulates breathing in response to changes in CO2/H+. This mechanism is essential for maintaining breathing unconsciously and its disruption is associated with breathing problems particularly during sleep. The lateral hypothalamus has long been considered a chemoreceptor region; however, mechanisms underlying this function are poorly understood. As LHA neurons show considerable genetic variability that may correlate with function, my central hypothesis is that discrete subsets of LHA neurons are specialized to function as respiratory chemoreceptors. To test this, I will use a novel genetic approach to label and identify CO2/H+ activated LHA neurons (Aim 1); identify intrinsic and synaptic mechanisms contributing to LHA CO2/H+ sensitivity (Aim 2), and determine contributions of these cells to baseline breathing and the ventilatory response to CO2 (Aim 3). Important outcomes of this work include 1) determining the cellular and network basis for how the LHA contributes to the CO2/H+ dependent breath, 2) inform about LHA functional heterogeneity, and 3) provide valuable training in molecular, cellular and whole animal approaches that should make me well positioned for taking the next step towards my goal of becoming an independent investigator.