The principal investigator of this mentored clinical science award is an anesthesiologist who is seeking advanced training in the physiology and pharmacology of general anesthetic action in native neurons. The long-term objectives of this proposal are two-fold. The first objective is to provide the principal investigator with the training that will allow her to become an independent medical scientist. The second objective is to understand the mechanism by which two general anesthetics cause clinically relevant changes in the sympathetic nervous system. The first objective will be obtained through mentored research and non-research activity including graduate classes in physiology and pharmacology. Training will be enhanced with weekly journal club, data review sessions departmental lecture series and interaction with colleagues. The second objective will be pursued with studies of general anesthetic activity at multiple levels of the sympathetic nervous system. General anesthetic modulation of the sympathetic nervous system allows the patient to undergo surgery without hemodynamic changes that would otherwise be detrimental. Modulation of postsynaptic sympathetic nAChRs will be studied using patch clamp recording of dispersed sympathetic ganglia neurons. General anesthetic activity at presynaptic nAChRs will be studied by monitoring the frequency of spontaneous synaptic transmission between dispersed sympathetic ganglia neurons and visceral motor neuron explants. The effects of anesthetics on excitatory input from the hypothalamus will be studied using patch clamp recording from dispersed hypothalamic neurons. The resulting information will provide understanding of the molecular mechanism underlying one of the anesthetic effects that limit anesthetic safety.
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