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Peer-reviewedCC BY-NC-ND 4.0Communications Biology

Control of synaptic communication through molecularly engineered bioluminescence light emission and sensing

6 affiliations
  1. 1Biochemistry, Cellular and Molecular Biology Graduate Program, Central Michigan University, Mt Pleasant, MI USA
  2. 2College of Medicine, Central Michigan University, Mt Pleasant, MI USA
  3. 3Neuroscience Program, Central Michigan University, Mt Pleasant, MI USA
  4. 4Department of Neurosciences, University of California San Diego, La Jolla, CA USA
  5. 5Carney Institute for Brain Science, Brown University, Providence, RI USA
  6. 6Department of Neuroscience, Brown University, Providence, RI USA

Abstract

Synapses are sites of intercellular communication between neurons and from neurons to target organs, and of signal integration that underly physiological and behavioral responses. We have developed a modular platform, Interluminescence (Int), for experimental control of synaptic transmission: bioluminescent light, generated by a luciferase oxidizing a luciferin, from a presynaptic neuron is used to activate transsynaptic optogenetic ion channels in the postsynaptic neuron. Two strategies can modulate postsynaptic neurons in the presence of luciferin. In the ‘Act-Int’ approach, a luciferase is genetically expressed in synaptic vesicles and released during depolarization-induced presynaptic vesicle fusion and exocytosis. In the ‘Persist-Int’ approach, a luciferase is tethered to the presynaptic membrane where it can support sustained transsynaptic signaling. Both strategies can activate postsynaptic neurons with comparable efficacy under the conditions tested. By design, the modularity of the platform permits the use of luciferases and opsins ranging in brightness and light sensitivity, with the luciferase targeted to different subcellular regions of the presynaptic neuron, and the postsynaptic opsin being excitatory or inhibitory. Our results demonstrate the utility and versatility of Interluminescence to mediate synaptic transmission that is either activity-dependent or activity-independent.

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BibTeX
@article{slaviero2026control,
  title = {{Control of synaptic communication through molecularly engineered bioluminescence light emission and sensing}},
  author = {Ashley N. Slaviero and Mansi Prakash and Rachel Schumaker and Emmanuel L. Crespo and Alexander D. Silvagnoli and Maya O. Tree and Gerard G. Lambert and Christopher I. Moore and Nathan C. Shaner and Diane Lipscombe and Ute Hochgeschwender},
  journal = {Communications Biology},
  year = {2026},
  month = jul,
  doi = {10.1038/s42003-026-10643-9},
  url = {https://doi.org/10.1038/s42003-026-10643-9},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Control of synaptic communication through molecularly engineered bioluminescence light emission and sensing
AU  - Ashley N. Slaviero
AU  - Mansi Prakash
AU  - Rachel Schumaker
AU  - Emmanuel L. Crespo
AU  - Alexander D. Silvagnoli
AU  - Maya O. Tree
AU  - Gerard G. Lambert
AU  - Christopher I. Moore
AU  - Nathan C. Shaner
AU  - Diane Lipscombe
AU  - Ute Hochgeschwender
PY  - 2026
DA  - 2026/07/10
JO  - Communications Biology
DO  - 10.1038/s42003-026-10643-9
UR  - https://doi.org/10.1038/s42003-026-10643-9
AB  - Synapses are sites of intercellular communication between neurons and from neurons to target organs, and of signal integration that underly physiological and behavioral responses. We have developed a modular platform, Interluminescence (Int), for experimental control of synaptic transmission: bioluminescent light, generated by a luciferase oxidizing a luciferin, from a presynaptic neuron is used to activate transsynaptic optogenetic ion channels in the postsynaptic neuron. Two strategies can modulate postsynaptic neurons in the presence of luciferin. In the ‘Act-Int’ approach, a luciferase is genetically expressed in synaptic vesicles and released during depolarization-induced presynaptic vesicle fusion and exocytosis. In the ‘Persist-Int’ approach, a luciferase is tethered to the presynaptic membrane where it can support sustained transsynaptic signaling. Both strategies can activate postsynaptic neurons with comparable efficacy under the conditions tested. By design, the modularity of the platform permits the use of luciferases and opsins ranging in brightness and light sensitivity, with the luciferase targeted to different subcellular regions of the presynaptic neuron, and the postsynaptic opsin being excitatory or inhibitory. Our results demonstrate the utility and versatility of Interluminescence to mediate synaptic transmission that is either activity-dependent or activity-independent.
SN  - 2399-3642
ER  -