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Amit Agarwal, Ph.D.
Activity Dependent Regulation of Astrocyte Function in Neural Circuits
Postdoctoral Fellow, Department of Neuroscience, Johns Hopkins University
2 Riverside Circle, Roanoke, VA 24016
In a mouse, a single astrocyte modulates and supports the function of ~100,000 synapses (in a human, the numbers increase to ~2 million synapses per astrocyte), and makes contact with several blood vessels and nodes of Ranvier. These elaborate connections made by fine astrocyte processes form functionally isolated and specialized compartments referred to as “microdomains.” Astrocytes communicate with the neighboring cells through complex Ca2+ signaling pathways and respond to the neuronal activity by releasing gliotransmitters and energy substrates. Several studies indicate that acute brain injury and neurodegeneration can induce aberrant Ca2+ signaling in astrocytes, demonstrating that this signaling is highly adaptable. However, little is known about the downstream molecular and cellular pathways regulated by this mode of signaling. Dr. Agarwal’s recent studies indicate astrocyte Ca2+ transients are generated by the cross talk between mitochondria and ER, which potentially enable coupling between ATP production and Ca2+ signaling events. Using novel mouse genetics tools, as well as advanced microscopic and physiological techniques, Dr. Agarwal proposes studying: (1) the structural and functional significance of microdomains, (2) mitochondrial dynamics and function in astrocytes, and (3) how neuronal activity modulates astrocyte function. Dr. Agarwal’s long-term goal is to decipher the basic principles by which neurons and astrocytes functionally integrate into the neural circuits and to identify molecular pathways that determine the transient or permanent nature of these cellular interactions. He will discuss plans for further elucidating the functional significance of these connections, and their role in learning, memory, and cognition.