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Amit Agarwal, Ph.D.
Decoding Microdomain Calcium Signaling in Astrocytes
Postdoctoral Fellow, Department of Neuroscience, Johns Hopkins University
2 Riverside Circle, Roanoke, VA 24016
The mammalian brain consists of two equal populations of broadly classified groups of cells called neurons and glia. The proper establishment and maintenance of connections between neurons and glia are essential for the millisecond precision of synaptic transmission. However, the mechanisms by which neurons connect and communicate with neighboring glia to assemble a functional and conscious brain are not well understood. This can be partly attributed to the fact that unlike neurons, glia do not exhibit electrical excitability, and the widely used electrophysiological methods to probe the connectivity of neurons are not ideal for studying these cells. But, glial cells exhibit a distinct form of excitability based on variation in intracellular Ca2+ concentrations. Although glial Ca2+ transients were discovered more than two decades ago, the mechanisms that generate them and their function in the brain remain a mystery. Recent advances in genetically encoded Ca2+ sensors and in vivo 2-photon microscopy is changing the landscape of glial biology. To study Ca2+ signals in astrocytes, one of most numerous glial cells type, Dr. Agarwal combines novel mouse genetics tools, advanced microscopic techniques, and computational methodologies. He investigates the mechanisms that generate Ca2+ signals in astrocytes and deciphers the downstream cellular processes regulated by them. During these studies, he has uncovered a novel pathway by which neuromodulators, such as norepinephrine, regulate astrocyte Ca2+ signals and stimulate mitochondrial ATP production in anticipation of increased metabolic demand. This finding defines a key aspect of astrocyte physiology and reveals new mechanisms of regulation of brain metabolism.