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Article
Nature Methods 2, 837 - 843 (2005)
Published online: 21 October 2005; | doi:10.1038/nmeth793

Rapid neurotransmitter uncaging in spatially defined patterns

Shy Shoham1, 2, 4, 5, Daniel H O'Connor1, 2, 5, Dmitry V Sarkisov2, 3 & Samuel S-H Wang1, 2

1  Department of Molecular Biology, Lewis Thomas Laboratory, Washington Road, Princeton University, Princeton, New Jersey 08544, USA.

2  Program in Neuroscience, Lewis Thomas Laboratory, Washington Road, Princeton University, Princeton, New Jersey 08544, USA.

3  Department of Physics, Lewis Thomas Laboratory, Washington Road, Princeton University, Princeton, New Jersey 08544, USA.

4  Present address: Faculty of Biomedical Engineering, Technion 32000, Haifa, Israel.

5  These authors contributed equally to this work.

Correspondence should be addressed to Samuel S-H Wang sswang@princeton.edu

Light-sensitive 'caged' molecules provide a means of rapidly and noninvasively manipulating biochemical signals with submicron spatial resolution. Here we describe a new optical system for rapid uncaging in arbitrary patterns to emulate complex neural activity. This system uses TeO2 acousto-optical deflectors to steer an ultraviolet beam rapidly and can uncage at over 20,000 locations per second. The uncaging beam is projected into the focal plane of a two-photon microscope, allowing us to combine patterned uncaging with imaging and electrophysiology. By photolyzing caged neurotransmitter in brain slices we can generate precise, complex activity patterns for dendritic integration. The method can also be used to activate many presynaptic neurons at once. Patterned uncaging opens new vistas in the study of signal integration and plasticity in neuronal circuits and other biological systems.

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Nature Methods
ISSN: 1548-7091
EISSN: 1548-7105
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