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Caged compounds are molecules whose activity is controlled by light. They are temporarily inactivated by being bound to a chemical group (the “cage” moiety). By breaking this bond with visible or infrared light, the molecules can be “uncaged” and activated.
Caged neurotransmitters are valuable tools for neuroscientists because the light activation means there is full control over the timing, location and amplitude of neurotransmitter release.
RuBi-Glutamate is a novel caged-glutamate compound based on ruthenium photochemistry, which allows for clean and fast photorelease and higher specificity than previous caged glutamate compounds. RuBi-Glutamate enables the activation of neuronal dendrites and circuits with visible or two-photon light sources, achieving precision at the level of single cells and dendritic spines1. View datasheet.
Figure 1. RuBI-Glutamate structure and its specificity for glutamate receptors in coronal slices from C57BL/6 mice. (A) The structure of RuBi-Glutamate showing how it uncages after light activation. (B) Depolarization caused by RuBi-Glutamate uncaging can be effectively and reversibly blocked by glutamate receptor antagonists AP5 (40 µM) and CNQX (20 µM). (C) A representative current–voltage (I-V) curve showing the uncaging response of RuBi-Glutamate. Note how it reverses at +10 mV indicating that the responses are mediated by glutamate receptors. (Figure adapted from Fino et al., 2009).
RuBi-GABA is a novel caged-GABA compound that uses a ruthenium complex as photosensor. It can be excited with visible wavelengths therefore providing the advantages of greater tissue penetration, less photo-toxicity, and faster photo-release kinetics than other UV light-sensitive caged compounds. It is suitable for GABA receptor mapping, and optical silencing of neuronal firing2. View datasheet.
Figure 2. RuBi-GABA structure induction of GABA receptor-mediated currents in mouse pyramidal neurons (A) Structure of Rubi-GABA showing light-induced uncaging. (B) Uncaging responses of RuBi-GABA recorded at different holding potentials (every 10 mV from 0 to -60 mV) showing reversal close to the expected chloride reversal (-43 mV). The black bar indicates the laser pulse. (C) Current-voltage (I-V) curve with a linear fit. (D) Average RuBi-GABA uncaging response before (top), during 20 µM gabazine application (center) and after drug wash-out (bottom). Responses were collected at -70 mV of holding potential in K+-based internal solution with -40 mV chloride reversal. The black bar indicates the laser pulse. Scale bars: 10 pA, 50 ms. (Figure adapted from Verde et al., 2008).
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1. Fino E, Araya R, Peterka DS, Salierno M, Etchenique R, Yuste R. RuBi-Glutamate: Two-Photon and Visible-Light Photoactivation of Neurons and Dendritic spines. Front Neural Circuits. 2009 May 27;3:2.