New optical control platform blocks and restores neural signaling

DGIST (President Kunwoo Lee) announced that a research team led by Professor Ji Won Um of the Center for Synapse Diversity and Specificity, Department of Brain Sciences, in collaboration with a research team led by Professor Alice Ting at Stanford University, has developed LATeNT, a novel optical control platform that uses light to block signal transmission between neurons and subsequently restore normal signaling. The technology is expected to be widely applicable to a broad range of life science and medical research, including elucidating the pathogenic mechanisms of brain disorders and regulating insulin secretion.

Synapses are the primary sites of connection through which neurons exchange information. Dysfunction of synaptic signaling can cause a wide range of neuropsychiatric disorders, including anxiety disorders, depression, and autism spectrum disorder. Conventional optogenetic technologies have largely been limited to controlling the electrical activity of neurons, with technical limitations in suppressing signal transmission at specific synapses for extended periods while allowing it to be fully restored afterward.

To overcome these limitations, the research team precisely designed LATeNT by fusing a light-oxygen-voltage (LOV) protein, which senses light, to tetanus neurotoxin that cleaves proteins involved in neurotransmitter release. LATeNT suppresses synaptic signaling by cleaving VAMP2, a protein essential for neurotransmission, only when exposed to blue light of a specific wavelength. Once the light stimulus is removed, it exhibits reversible properties with neurotransmission naturally returning to its original state within approximately 24 hours.

In particular, LATeNT induces a strong inhibitory effect on neurotransmission with only weak blue-light stimulation. Applying this in a mouse model, the research team transiently blocked signaling from specific inhibitory neurons in the hippocampus, which regulates memory and emotion, and demonstrated that these neurons are instrumental in the neural circuits in the brain controlling anxiety-related behavior. Moreover, LATeNT exhibited stronger and more sustained inhibitory effects than conventional optogenetic tools.

Furthermore, the research team applied LATeNT to the central nervous system, as well as pancreatic β cells, succeeding in precisely regulating insulin secretion using light. These findings suggest that LATeNT is a versatile platform with broad applicability across biotechnology transcending brain neural circuit research, including research on metabolic and immune disorders and the design of synthetic biology-based genetic circuits.

LATeNT is the first molecular tool that can spatiotemporally control the function of specific synaptic proteins, significantly enhancing the precision of neural circuit research. When combined with AAV (adeno-associated virus) gene delivery technology or drug control systems in the future, it could be expanded into a platform for personalized precision therapy applicable not only to brain and neurological disorders but also to cancer, metabolic disorders, and immune disorders."

Professor Ji Won Um, Center for Synapse Diversity and Specificity, Department of Brain Sciences

This research was jointly conducted by the Center for Synapse Diversity and Specificity at DGIST Department of Brain Sciences with Stanford University, supported by the Ministry of Science and ICT and the National Research Foundation of Korea. Dr. Heegwang Roh and Dr. Dongwook Kim participated as co-first authors, and the findings were published online on July 31, 2026, in Nature Methods, a prestigious journal in the field (top 0.6% in its JCR category; impact factor: 28.3).