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Our primary objective is to determine the mechanisms of neural plasticity with chronic hypoxia, and specifically the physiological mechanisms of ventilatory acclimatization to chronic hypoxia, in the respiratory centers and chemoreceptors of the central nervous system (CNS). Experiments use: (1) rats and transgenic mice to measure breathing and arterial blood gases in a conscious unrestrained animal model; (2) anesthetized rats to isolate the role of the CNS by measuring the phrenic nerve response to electrical stimulation of the sensory nerve from carotid body chemoreceptors; (3) immunohistochemistry and quantitative RT-PCR, and (4) stereotaxic microinjections of glutamate, GABA and dopamine agonists and antagonists to study neurotransmitter receptor plasticity; (6) saporin conjugate microinjections to lesion specific neuronal phenotypes, and (7) transgenic mice with conditional gene deletions for hypoxic sensitive genes (e.g. HIF-1Ą) using the Cre-loxP system with tissue-specific promoters or adeno-associated virus.

Track(s):
Physiology