Nippert, Amy2022-01-042022-01-042021-10https://hdl.handle.net/11299/225887University of Minnesota Ph.D. dissertation. October 2021. Major: Neuroscience. Advisor: Eric Newman. 1 computer file (PDF); iv, 96 pages.Hypoglycemia causes increases in cerebral blood flow (CBF). Astrocytes play a key role in the regulation of basal arteriole diameter under resting conditions and during pathology. However, the contribution of astrocyte signaling to hypoglycemic alterations of CBF is unknown. We hypothesized that astrocyte calcium signaling increases in response to hypoglycemia and that this calcium increase leads to the release of vasodilators and contributes to arteriole dilation during hypoglycemia. We further hypothesized that changes in vessel state during hypoglycemia alters neurovascular coupling, the response of vessels to neuronal activity. We found that during hypoglycemia, astrocyte calcium signaling was increased. This increase in calcium signaling was eliminated in the presence of an A2 adenosine receptor antagonist, which also decreased the hypoglycemia-evoked arteriole dilation. Hypoglycemia-induced arteriole dilation was also reduced in IP3R2 KO mice, which have reduced calcium signaling. Pharmacological inhibition of prostaglandins and epoxyeicosatrienoic acids, potent vasodilators that are released by astrocytes, also reduced arteriole dilation during hypoglycemia. To test the effect of hypoglycemia on neurovascular coupling, a whisker puff stimulus was used to look at evoked neuronal activity and arteriole dilation. During hypoglycemia, both stimulus evoked neuronal activity and stimulus evoked arteriole dilation were reduced, and neurovascular coupling remained constant. These results support the hypothesis that hypoglycemia-induced increases in brain adenosine mediate increases in astrocyte calcium signaling and that astrocytes contribute to hypoglycemic vasodilation in a calcium-dependent manner. Hypoglycemia also decreases stimulus-evoked neuronal responses, perhaps through an adenosine dependent mechanism, but neurovascular coupling is unchanged.enNeurosciencesThesis or Dissertation