Michael J. Schell, Ph.D., Assistant Professor
Ph.D., Neuroscience, Johns Hopkins Halim ND, McFate T, Mohyeldin M, Okagaki P, Korotchkina LG, Patel MS, Jeoung MH, Harris RA, Schell MJ, and Verma A. (2010). Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of rat cerebral cortical astrocytes and neurons. Glia (in press)
Postdoctoral, Pharmacology, Cambridge, UK
Email: mschell@usuhs.mil
The brain encodes sensory experiences in less than a second, yet often maintains memories for a lifetime. How vast ensembles of brain cells accomplish this remarkable feat is one of the most fundamental questions in neuroscience. Pyramidal neuron dendrites are covered with protrusions called dendritic spines, which are the postsynaptic receiving points for excitatory signals from other neurons. The molecular architecture of spines undergoes rapid modification during learning, and how these changes consolidate and form memories is unknown. Spines isolate calcium signals of high dynamic range inside microdomains, and this process somehow integrates synaptic input over timescales of milliseconds to seconds. Over longer timescales, spines change their connectivity, shape, and number, and this reflects a type of structural plasticity that underlies long-term memory storage. ? We are studying on how calcium signals influence spine structure through their ability to regulate the actin cytoskeleton. To do this we focus on hippocampal pyramidal neurons, and we rely heavily on live cell imaging. To visualize the actin cytoskeleton in spines, we visualize the enzyme inositol trisphosphate 3-kinase A (ITPKA), which is enriched in spines because of a unique N-terminal domain that binds to the sides of a dynamic pool of actin filaments concentrated there. ITPKA itself influences calcium signals because it phosphorylates the second messenger inositol trisphosphate (IP3) and thereby turns off the signal to release calcium from intracellular stores. The goal of the research is to reveal the molecular pathways by which synaptic calcium signals influence the activity of proteins that regulate the actin microstructure in spines-and to understand the consequences of persistent molecular and structural change at the synapse on learning and memory.
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Schell MJ (2010). Inositol trisphosphate 3-kinases: Focus on immune and neuronal signaling. Cell Mol Life Sci. 67:1755-1778.
Johnson HW and Schell MJ (2009). Neuronal IP3 3- kinase is an F-actin bundling protein: Role in dendritic targeting and regulation of spine morphology. Molec. Biol. Cell. 20:5166-5180
Letcher AJ, Schell MJ, and Irvine RF (2008). Do mammals make all their own inositol hexakisphosphate? Biochem. J. 416:263-270.
Lloyd-Burton SM, Yu JC, Irvine RF, and Schell MJ (2007). Regulation of Ins(1,4,5)P3 3-kinases by calcium and localization in cells. J. Biol Chem. 282:9526-9535
Schell MJ and Irvine RF (2006). Calcium-triggered exit of IP3 3-kinase A and F-actin from dendritic spines is rapid and reversible. Eur. J. Neurosci. 24:2491-2503
Complete list of publications click here
Schell lab microscopy videos
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