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Two-photon uncaging of γ-aminobutyric acid in intact brain tissue

Nature Chemical Biology volume 6, pages 255–257 (2010)Cite this article

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Abstract

We have synthesized a photosensitive (or caged) 4-carboxymethoxy-5,7-dinitroindolinyl (CDNI) derivative of γ-aminobutyric acid (GABA). Two-photon excitation of CDNI-GABA produced rapid activation of GABAergic currents in neurons in brain slices with an axial resolution of approximately 2 μm and enabled high-resolution functional mapping of GABA-A receptors. Two-photon uncaging of GABA, the main inhibitory neurotransmitter, should allow detailed studies of receptor function and synaptic integration with subcellular precision.

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Figure 1: Functional mapping of GABA sensitivities in the perisomatic dendritic area of a hippocampal neuron by 2P photolysis of CDNI-GABA.
Figure 2: Functional mapping of GABA-A receptors on the proximal apical dendrites and the axon initial segment.

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Acknowledgements

This work was supported by US National Institutes of Health grant GM53395 (to G.C.R.E.-D.), a Grant-in-Aid for Scientific Research on Priority Areas (Elucidation of neural network function in the brain, number 20021008, to M.M.), a Grant-in-Aid for Young Scientists (A) (number 19680020, to M.M.) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, and funding from Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (to M.M.).

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Author notes

  1. Masanori Matsuzaki and Graham C R Ellis-Davies: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Masanori Matsuzaki, Tatsuya Hayama & Haruo Kasai

  2. Center for NanoBio Integration, University of Tokyo, Tokyo, Japan

    Masanori Matsuzaki, Tatsuya Hayama & Haruo Kasai

  3. Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Graham C R Ellis-Davies

Authors
  1. Masanori Matsuzaki
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  2. Tatsuya Hayama
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  3. Haruo Kasai
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  4. Graham C R Ellis-Davies
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Contributions

G.C.R.E.-D. made and characterized the caged compounds. M.M. and T.H. performed biological experiments and analyzed the data. H.K. provided resources and support for the biological experiments. G.C.R.E.-D. and M.M. wrote the manuscript.

Corresponding authors

Correspondence to Masanori Matsuzaki or Graham C R Ellis-Davies.

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Competing interests

G.C.R.E.-D. has filed a patent on dinitroindolinyl caged compounds.

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Supplementary Methods, Supplementary Figures 1–3 and Supplementary Table 1 (PDF 798 kb)

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Matsuzaki, M., Hayama, T., Kasai, H. et al. Two-photon uncaging of γ-aminobutyric acid in intact brain tissue. Nat Chem Biol 6, 255–257 (2010). https://doi.org/10.1038/nchembio.321

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