Optochemical Control of the Neuron-Astrocyte Circuit

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Astrocytes are star-shaped glial cells in the brain and spinal cord. They are connective tissue cells of the nervous system that link nerve cells to blood vessels and, by wrapping round brain capillaries, help to form the blood-brain barrier. Understanding of astrocyte signaling seriously lags in comparison with that of neurons, because the astrocytes are not electrophysiologically active. It is not known what extracellular signals astrocytes respond to and how they contribute to circuit function. The research proposed by Poskanzer has the promise of elucidating these key questions. The research has high potential to gain new insight and scientific knowledge. Neural circuits involve many cell types, although the vast majority of circuit studies neglect to take into account the non-neuronal glial cells in the brain. This proposal addresses gaps in our understanding of glial cells in neural circuit function and harnesses the power of light-activatable tools to tackle them. The PI applies a suite of optochemical tools that allow spatiotemporally precise and physiologically relevant release of neurotransmitter to astrocytes and neurons in cortical brain circuits. Compounds promising for research will be made available to the scientific community, and many collaboration opportunities are available at USCF. The PI proposes to use ruthenium-bipyridine (RuBi) cages to deliver neurotransmitters to astrocytes by photo-activation and monitoring the response from Ca++ activity in their branches by a genetically encoded Ca++ indicator using a second laser. She will test the hypothesis that astrocytes can respond to neurotransmitters and whether astrocytes can be activated in vivo. This proposal investigates the very fundamental question of how astrocytes respond to a range of neurotransmitters. Novel compounds will be developed to deliver controllable concentrations of neurotransmitters to cells. Calcium response will be monitored and astrocyte response will be studied as concentration is varied. Following initial in-vitro testing in brain slices. She will test the hypothesis that astrocytes can respond to neurotransmitters and whether astrocytes can be activated in-vivo in mice.The PI has a unique international collaboration with the Etchenique lab in Argentina and is enthusiastic about introducing biology students to imaging techniques, as evidenced by the relevant Cellular and Molecular Neuroscience course and the position with the Woods Hole Marine Lab. Undergraduate students will be involved through the USCF summer research program, and K-12 outreach through the science and health education partnership.