Optogenetic pharmacology for control of native neuronal signaling proteins

Abstract

The optical neuroscience revolution is transforming how we study neural circuits. By providing a precise way to manipulate endogenous neuronal signaling proteins, it also has the potential to transform our understanding of molecular neuroscience. Recent advances in chemical biology have produced light-sensitive compounds that photoregulate a wide variety of proteins underlying signaling between and within neurons. Chemical tools for optopharmacology include caged agonists and antagonists and reversibly photoswitchable ligands. These reagents act on voltage-gated ion channels and neurotransmitter receptors, enabling control of neuronal signaling with a high degree of spatial and temporal precision. By covalently attaching photoswitch molecules to genetically tagged proteins, the newly emerging methodology of optogenetic pharmacology allows biochemically precise control in targeted subsets of neurons. Now that the tools for manipulating endogenous neuronal signaling proteins are available, they can be implemented in vivo to enhance our understanding of the molecular bases of brain function and dysfunctions.

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Figure 1: Photochemical tools for controlling neural function.
Figure 2: Three methods of photocontrol for mapping mechanisms of brain function.
Figure 3: Optogenetic pharmacology enables photocontrol of ion channels and neurotransmitter receptors in mouse hippocampal neurons.
Figure 4: Expression options for optogenetic pharmacology.

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Acknowledgements

This work was supported by grants to R.H.K. from the National Eye Institute and the US National Institutes of Health.

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Correspondence to Richard H Kramer.

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Kramer, R., Mourot, A. & Adesnik, H. Optogenetic pharmacology for control of native neuronal signaling proteins. Nat Neurosci 16, 816–823 (2013). https://doi.org/10.1038/nn.3424

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