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Cloaked caged glutamate eliminates off-target GABA-A receptor antagonism and opens a new door in neuroscience

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Caged neurotransmitters are widely used to study neurobiological processes such as synaptic transmission and plasticity. However, uncaging has been primarily restricted to in vitro and ex vivo experimental systems. Using caged neurotransmitters in vivo has posed a huge hurdle because photoactivatable cages bind to GABA-A receptors, acting as competitive antagonists towards GABA. This reduced inhibition leads to epileptiform-like activity, which can cause problems for circuit level studies in vivo. To circumvent this off-target effect, a recent publication introduces a new caged glutamate: G5-MNI-glutamate. Using a novel technique called ‘cloaking,’ GABA-A receptor antagonism is abolished, opening up new possibilities for future in vivo studies with caged neurotransmitters.

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Fig. 1: Cloaked G5-MNI-glutamate abolishes the GABA-A receptor antagonism of MNI-glutamate.

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Acknowledgements

This work was supported by a NARSAD Young Investigator Award (W.C.O.) and a Neuroscience Training Grant T32 NS099042 (R.O.).

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Authors and Affiliations

  1. Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA

    Roberto Ogelman, In-Wook Hwang & Won Chan Oh

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  1. Roberto Ogelman
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  2. In-Wook Hwang
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  3. Won Chan Oh
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Correspondence to Won Chan Oh.

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Ogelman, R., Hwang, IW. & Oh, W.C. Cloaked caged glutamate eliminates off-target GABA-A receptor antagonism and opens a new door in neuroscience. Lab Anim 49, 177–179 (2020). https://doi.org/10.1038/s41684-020-0555-8

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