Long-term editing of brain circuits using an engineered electrical synapse
type: NewsArticle
description: Researchers engineered a synthetic electrical synapse using two connexin proteins from white perch fish, connexin 34.7 and connexin 35, to enable precise modulation of mammalian neural circuits. Through protein mutagenesis and computational modeling, they identified a structural motif that allows these connexins to dock selectively with each other without interacting with mammalian connexins, preventing off-target connections. This approach, called "long-term integration of circuits using connexins" (LinCx), was validated in worms and mice, demonstrating its ability to strengthen communication between specific cell types and modify behavior.
date published: 2026-05-17T20:46:57+00:00
date modified: 2026-05-20T22:36:02+00:00
language: en
is accessible for free: true
article body: ## Abstract Electrical signalling across distinct populations of brain cells underpins cognitive and emotional function. However, approaches that selectively regulate electrical signalling between two cellular components of a mammalian neural circuit remain sparse. Here we engineered an electrical synapse composed of two connexin proteins 1 found in *Morone americana*(white perch fish)—connexin 34.7 and connexin 35—to accomplish mammalian circuit modulation. By exploiting protein mutagenesis, devising a new in vitro system for assaying connexin hemichannel docking, and performing computational modelling of hemichannel interactions, we uncovered a structural motif that contributes to electrical synapse formation. Targeting this motif, we designed connexin 34.7 and connexin 35 hemichannels that dock with each other to form an electrical synapse but not with other major connexins expressed in the mammalian central nervous system. We validated this electrical synapse in vivo using worms ( *Caenorhabditis* *elegans*) and mice ( *Mus musculus*). We demonstrate that it can strengthen communication across neural circuits composed of pairs of distinct cell types and modify behaviour accordingly. Thus, we establish ‘long-term integration of circuits using connexins’ (LinCx) for precision circuit editing in mammals. ### Similar content being viewed by others ## Main Electrical synapses enable the direct flow of ions and small molecules between two cells and play a prominent part in coupling electrical activity in multiple organs, including the brain 2,3,4. Electrical synapses comprise multiple gap junction channels, each composed of two docked hemichannels embedded in the membranes of two touching cells. Each hemichannel is an oligomer that consists of six monomeric proteins called connexins, of which there are 21 isoforms in humans . Most connexins can form single-isoform hemichannels that dock with themselves to create homotypic gap junctions (Fig. [5](/articles/s41586-026-1…
publisher: Web Pulse
keywords: research, science
mentions: Morone americana
mentions: connexin 34.7
mentions: connexin 35
mentions: Caenorhabditis elegans
mentions: Mus musculus
mentions: LinCx
citation: CreativeWork