Light-activated tool reversibly silences specific synapses in living mice

Researchers at the Daegu Gyeongbuk Institute of Science and Technology and Stanford University have developed LATeNT, a molecular tool that uses light to temporarily halt signal transmission at specific synapses. The system fuses a light-sensitive LOV protein to tetanus neurotoxin, enabling precise cleavage of VAMP2, a protein essential for neurotransmitter release, only when illuminated with blue light.

Unlike conventional optogenetics, which typically modulate neuronal firing, LATeNT targets the synaptic machinery directly, allowing researchers to silence communication between defined neuron populations without killing the cells. After the light stimulus is removed, synaptic function recovers spontaneously within approximately 24 hours as new VAMP2 protein is synthesized.

In cultured neurons, blue-light exposure triggered rapid VAMP2 cleavage and suppressed neurotransmission. In mice, the team delivered LATeNT via adeno-associated virus to inhibitory neurons in the hippocampus, a region involved in memory and emotion. Brief blue-light stimulation silenced these neurons and altered anxiety-related behaviors, demonstrating that the tool can interrogate specific circuit functions in vivo.

The researchers report that LATeNT produced stronger and more sustained inhibition than existing optogenetic silencers. Beyond the nervous system, the platform also regulated insulin secretion when expressed in pancreatic beta cells, indicating potential utility in metabolic research.

The study, published in Nature Methods, describes LATeNT as the first tool capable of spatiotemporally controlling a specific synaptic protein in living animals. The authors suggest that combining the system with viral gene delivery or drug-inducible systems could eventually enable precise therapeutic interventions for neurological, metabolic, and immune disorders.

The work remains at the experimental stage; the paper notes that recovery kinetics and long-term effects of repeated cleavage cycles require further characterization. No human applications have been tested.