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Selective control of synaptically-connected circuit elements by interluminescence

Description

Abstract:
A wealth of new tools can directly control output of specific neurons on fast (e.g., optogenetic) or sustained (e.g., chemogenetic) time scales. In contrast, almost no methods exist for selectively modulating communication between defined cells at the synaptic level, which is key to understanding how functional connectivity creates percepts, engrams and actions. Here, we advance a novel strategy for selectively modulating synaptic transmission, Inter-luminescence. This approach uses bioluminescent light from a presynaptic axon terminal, generated by a luciferase, to modulate an opsin in its postsynaptic target under experimenter-controlled introduction of a small molecule (luciferin). We developed two separate methods that target the luciferase to the synaptic cleft. To provide sustained and synapse-specific regulation, the ‘Persist-Int’ strategy places a luciferase in the synaptic cleft tethered to the presynaptic terminal, and an opsin in the opposing postsynaptic membrane. In this configuration, light generation creates sustained and activity-independent modulation. In the complementary ‘Act-Int’ strategy, luciferase is released into the synaptic cleft in response to presynaptic activity, a synapse-specific form of activity-dependent modulation.
Notes:
This research was supported by the the National Science Foundation (NSF) and its Division of Biological Infrastructure under Award No. 1707352 and the National Institutes of Health under award no. NIH R01NS120832 and the W. M. Keck Foundation

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Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
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In Copyright

Citation

Hochgeschwender, Ute, Shaner, Nathan C., and Moore, Christopher I., "Selective control of synaptically-connected circuit elements by interluminescence" (2021). NeuroNex Data and Research Products. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/5n5r-2f66

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  • NeuroNex Data and Research Products

    This collection contains publicly available research products, including data, codes, and publications, among others. The NeuroNex Technology Hub is supported by the National Science Foundation (NSF) and its Division of Biological Infrastructure under Award No. 1707352.
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