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- Flashy Science: Controlling Neural Function with Light


Flashy Science: Controlling Neural Function with Light

Scott M. Thompson,1Joseph P. Y. Kao,1,2Richard H. Kramer,3Kira E. Poskanzer,4R. Angus Silver,5David Digregorio,5 and Samuel S.-H. Wang6

1Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, 21201, 2Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, 3Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, 4Department of Biochemistry, University of California, San Francisco, San Francisco, California 94143, 5Department of Physiology, University College, London WC1E 6BT, United Kingdom, and 6Department of Molecular Biology and Program in Neuroscience, Princeton University, Princeton, New Jersey 08544

Key words: photolysis; caged molecule; glutamate uncaging; photostimulation; activity; photoinactivation

One of the most powerful means for studying the function of proteins, synapses, cells, and networks of cells is to control their activation in time and in space. Many commonly used approaches are inadequate for some experimental questions. Modulation of protein function by traditional genetic approaches depends on natural protein turnover, which occurs on a sufficiently slow timescale to permit homeostatic compensation by other proteins. Synapses and cells are usually activated electrically, with stimuli delivered by wire or glass electrodes, or chemically, by applying exogenous neurotransmitters and other modulatory substances. The spatial, temporal, and molecular resolution of these approaches is limited, however. Moreover, the precise anatomical location of the synapses activated by electrical stimuli are generally unknown. Application of receptor agonists for only brief periods in a manner that mimics naturally occurring transmitter release can only be performed with isolated cells and membrane patches but is difficult in more intact preparations. For cells within networks, inactivating them with traditional lesioning approaches is irreversible, difficult to localize to small or distinct cell populations, and often accompanied by damage to fibers of passage. Finally, it is difficult to control the function of individual cells in complex tissues or of individual proteins in complex signaling cascades.

The development of technology to observe changes in the intracellular concentration of Ca2+ and other ions with fluorescence microscopy has increased our knowledge of cellular and synaptic function enormously. Recent advances in microscopy, optical physics, laser instrumentation, and molecular probe development have now engendered methodology that permits not only the observation but also the simultaneous manipulation of neural function with unprecedented spatial and temporal resolution through the use of light. In this mini-symposium, some practitioners of this emergent technology will highlight the state of the art in the development and application of new techniques in this rapidly advancing field. In particular, improvements in microscopy, photonics, and laser "hardware," as well as results obtained using newly developed "software," such as novel chemically synthesized and genetically encoded light-sensitive probes, are illustrated.

Source: The Journal of Neuroscience, November 9, 2005, 25(45):10358-10365.

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