Study of the function and structure of single inhibitory synapses revealed by two-photon uncaging of GABA

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We have synthesized a photosensitive CDNI derivative of GABA. Two-photon excitation of CDNI-GABA produced rapid activation of GABAergic currents in neurons in brain slices with an axial resolution of approximately 2μm and enabled high-resolution functional mapping of GABA-A receptors. In addition, we developed another caged GABA, DCAC-GABA, which, when combined with an appropriate caged glutamate, allows bimodal control of neuronal membrane potential with subcellular resolution using optically independent two-photon uncaging of each neurotransmitter. We used two-color, two-photon uncaging to fire and block action potentials from rat hippocampal CA 1 neurons in brain slices with 720-nm and 830-nm light, respectively. Our method should be generalizable to other chemical messenger pairs.