The goal of proposal is the development and testing of new optical technology for two- photon uncaging of neurotransmitters. The caged neurotransmitters developed we have previously made have been widely used by many research groups around the world. An important feature of our work is that we have forged long-term collaborative relationships with noted physiologists. These interactions have been vital the development of useful and important caged compounds as it is the biological problems that define the probes. In this proposal we seek to address an important gap in the area of optical chemical methods that are used for photochemical probing of neuronal function, namely, the ability to accomplish simultaneous, multimodal optical control of parallel signaling processes. In the previous grant cycle we made new caging that chromophore that can be photolyzed with almost complete chromatic selectivity at long wavelengths of light, whilst being essential photostable at short wavelengths. We propose to apply this probe to test questions concerning the integration of excitatory and inhibitory signals in pyramidal cells. We will also continue to develop chemical probes looking at off-target pharmacological effects of caged compounds and develop new caged compounds with extended pi electron systems. The overall goal of this proposal is to develop new photochemical tools that allow bidirectional optical control of dendritic signaling processes.

Public Health Relevance

Optical methods are a primary technique for the study of cellular physiology. This research concerns the development of new optical probes that will enable simultaneous photocontrol of two neurotransmitter signaling systems for the first time. Since almost all cell signaling is bidirectional or symbiotic, these new methods will revolutionize our ability to control function and therefore uncover many fresh details of cell physiology.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Biophysics of Neural Systems Study Section (BPNS)
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Talley, Edmund M
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Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
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Passlick, Stefan; Ellis-Davies, Graham C R (2018) Comparative one- and two-photon uncaging of MNI-glutamate and MNI-kainate on hippocampal CA1 neurons. J Neurosci Methods 293:321-328
Passlick, Stefan; Richers, Matthew T; Ellis-Davies, Graham C R (2018) Thermodynamically Stable, Photoreversible Pharmacology in Neurons with One- and Two-Photon Excitation. Angew Chem Int Ed Engl 57:12554-12557
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Agarwal, Hitesh K; Janicek, Radoslav; Chi, San-Hui et al. (2016) Calcium Uncaging with Visible Light. J Am Chem Soc 138:3687-93
Sajo, Mari; Ellis-Davies, Graham; Morishita, Hirofumi (2016) Lynx1 Limits Dendritic Spine Turnover in the Adult Visual Cortex. J Neurosci 36:9472-8
Kantevari, Srinivas; Passlick, Stefan; Kwon, Hyung-Bae et al. (2016) Development of Anionically Decorated Caged Neurotransmitters: In Vitro Comparison of 7-Nitroindolinyl- and 2-(p-Phenyl-o-nitrophenyl)propyl-Based Photochemical Probes. Chembiochem 17:953-61

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