Control of Synaptic Communication through Molecularly Engineered Bioluminescence Light Emission and Sensing

Area of Science:

• Neuroscience
• Molecular Biology
• Biotechnology

Background:

• Synapses are crucial for neuronal communication and signal integration, underpinning physiological and behavioral responses.
• Existing methods for controlling synaptic transmission often lack modularity and precise spatial or temporal control.

Purpose of the Study:

• To develop and validate a modular platform, Interluminescence (Int), for experimental control of synaptic transmission.
• To enable transsynaptic optogenetic activation or silencing of postsynaptic neurons using bioluminescence.

Main Methods:

• Developed the Interluminescence (Int) platform utilizing luciferase-generated bioluminescence to activate optogenetic channels in postsynaptic neurons.
• Implemented two strategies: 'Act-Int' (luciferase in synaptic vesicles) and 'Persist-Int' (membrane-tethered luciferase).
• Demonstrated in vivo application for synapse-specific neuronal control.

Main Results:

• Both 'Act-Int' and 'Persist-Int' strategies effectively activated postsynaptic neurons with comparable efficacy.
• The modularity of Int allows for customizable combinations of luciferases and opsins with varying properties.
• Luciferase targeting to different subcellular presynaptic regions was feasible, enhancing experimental flexibility.

Conclusions:

• Interluminescence (Int) provides a versatile and modular platform for controlling synaptic transmission.
• The platform supports both activity-dependent and activity-independent synapse-specific neuronal activation.
• Int offers a powerful tool for advanced neuroscience research requiring precise control over neuronal circuits.