New Delhi: Researchers have developed a molecular tool called SynTrogo (Synthetic Trogocytosis) that allows for the physical rewiring of brain circuits. While previous technologies focused on modulating the electrical firing of the neurons, this new tool specifically targets the connectome, the physical network of synaptic junctions, by harnessing the natural pruning capacity of star-shaped cells in the brain known as astrocytes. Astrocytes are glial cells that maintain the neural environment. SynTrogo uses a lock-and-key mechanism to induce these cells to selectively remove synaptic material.
In this system, neurons are engineered to display a specific molecular tag, while astrocytes are equipped with a matching receptor. Upon contact, the astrocyte nibbles the neuronal membrane through a synthetic version of trogocytosis, the process by which a cell consumes small portions of another, effectively dismantling the target connection without altering the initial neuronal activity. The technology was tested on the hippocampus, a region of the brain critical for learning. The researchers were able to reduce synapse density by about 27 per cent. Despite the decrease in total connections, the remaining synapses underwent significant compensatory refinement. The surviving junctions became structurally larger, and functionally more efficient.
The tech has clinical potential
The structural editing resulted in enhanced cognitive performance in animal models. Mice with SynTrogo-modified circuits demonstrateed superior memory retention in fear-conditioning tests. Furthermore, the animals maintained cognitive flexibility, indicating that the reduced synapse count placed the circuit into a more plastic, learning-ready state. This breakthrough provides a foundation for connectome editing, a new strategy to investigate and potentially treat disorders characterised by synaptic dysfunction, such as Alzheimer’s diseases, schizophrenia and autism spectrum disorder. The findings indicatee that brain function is not necessarily maximised by the highest number of synapses, but rather by their organisation and the efficiency of those connections. A paper describing the research has been published in Nature Communications.