A """"""""caged"""""""" molecule is a photosensitive, but temporarily inert, precursor of a biologically active molecule. Absorption of light transforms the precursor into a molecule with full bioactivity. Because light can be easily focused and steered, and photochemical changes are fast, caged molecules represent a versatile tool for manipulating biology with light with high temporal and spatial control. The long-term objective of this project is to develop a broad spectrum of caged molecules that will allow cellular physiologists to use light to probe and control dynamic signaling processes in living cells and tissues. This proposal has four foci: 1) Develop new """"""""cages"""""""" that have a) strong light absorption in single- and two-photon applications, b) high yield of product molecules upon photolysis, c) fast kinetics of product photorelease, and d) high pre-photolysis stability. 2) Develop new caged probes of neural signaling including neurotransmitters, lipid mediators, and inhibitors of transmitter transport. 3) Develop two new specific probes of intracellular calcium signaling: an optimal caged calcium and a caged agonist for the ryanodine receptor. 4) Apply the newly developed tools in ongoing and emerging independent and collaborative research to explore four topics in cellular neurophysiology: dendritic signal processing, synaptic plasticity, shaping of the synaptic event by glia, and calcium regulation of excitability.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Cell Development and Function Integrated Review Group (CDF)
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Shapiro, Bert I
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University of MD Biotechnology Institute
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Meng, Xiangying; Winkowski, Daniel E; Kao, Joseph P Y et al. (2017) Sublaminar Subdivision of Mouse Auditory Cortex Layer 2/3 Based on Functional Translaminar Connections. J Neurosci 37:10200-10214
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Deng, Rongkang; Kao, Joseph P Y; Kanold, Patrick O (2017) Distinct Translaminar Glutamatergic Circuits to GABAergic Interneurons in the Neonatal Auditory Cortex. Cell Rep 19:1141-1150
Meng, Xiangying; Kao, Joseph P Y; Lee, Hey-Kyoung et al. (2017) Intracortical Circuits in Thalamorecipient Layers of Auditory Cortex Refine after Visual Deprivation. eNeuro 4:
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Meng, Xiangying; Kao, Joseph P Y; Lee, Hey-Kyoung et al. (2015) Visual Deprivation Causes Refinement of Intracortical Circuits in the Auditory Cortex. Cell Rep 12:955-64
Legenzov, Eric A; Sims, Stephen J; Dirda, Nathaniel D A et al. (2015) Disulfide-Linked Dinitroxides for Monitoring Cellular Thiol Redox Status through Electron Paramagnetic Resonance Spectroscopy. Biochemistry 54:6973-82
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