Have you ever thought about what it would be like to have a “switch” to turn off mental disorders like social anxiety or obsessive compulsive disorder? Maybe we are not that far off. A team of scientists from the dukeuniversity just took a giant leap by creating artificial electrical synapses in the brains of mice, changing the way their neurons communicate.
These gene-edited synapses bypassed problematic chemical connections, creating new signaling pathways that actually changed the animals' behavior. Mice genetically predisposed to develop behaviors similar to obsessive compulsive disorder (OCD) showed minimal symptoms and about two-thirds never developed typical facial lesions. A breakthrough that could represent the dawn of a new era for psychiatry.
Beyond Neurotransmitters: The Brain's Electrical Highways
In mammals, including humans, the brain communicates primarily through chemical synapses that use neurotransmitters. Electrical synapses, which are much rarer, rely instead on proteins called connexins. And this is what the brilliant intuition of Kafui Dzirasa and his team.
“We wanted to find out if we could engineer a way to bypass chemical synapses between cells by inserting an electrical synapse,” he explains. Dzirasa. It was no easy feat: while similar works had been conducted on the nematodes C. elegans (a worm with just 302 neurons), Mice have approximately 71 million neurons, a vastly superior level of complexity.
To create these new “neural highways,” researchers first had to identify the right connexins. The choice fell on connections 34.7 and 35, found in a fish called white perch. These proteins function like the positive and negative sides of an electrical circuit, allowing current to pass directly between neurons.
Artificial Synapses: Mapping the Brain to Intervene with Precision
The next challenge was to figure out where to place these new connections. The scientists implanted tiny electrodes into the brains of mice, creating an electrical map that showed the flow of information between different brain areas.
By observing how this map changed when the mice were exposed to anxiety- or aggression-inducing situations, the team could pinpoint the circuits to be modified. A harmless virus was then used to deliver the genetic information needed to produce connexins into target cells.
The result? Fully functional electrical synapses that altered the electrical flow in the frontal cortex, making mice more exploratory and sociable. A potentially revolutionary application for conditions such as social anxiety.
Preventing Mental Disorders, Not Just Curing Them
In a second, even more ambitious experiment, the researchers wanted to verify whether this technique could prevent the onset of psychiatric problems.
We have created an approach to modify the connection between cells, allowing for targeted rewiring of the brain. It has the potential to correct many different types of genetically induced wiring deficits to prevent the emergence of psychiatric disorders.
By targeting a long-range circuit between the frontal cortex and an area of the brain called the thalamus (important when mice are stressed), introducing electrical synapses improved communication between these regions, preventing the mice from “freezing” in response to stress.
Even more impressive was the experiment on mice genetically predisposed to develop OCD-like symptoms. Typically, these animals begin to groom themselves obsessively, to the point of causing facial lesions that resemble those of people with OCD who compulsively wash their hands. Mice equipped with artificial synapses groomed themselves less, and about two-thirds never developed lesions.
Artificial Synapses, the Future: Human Brain Editing?
Although the work was conducted on mice, Dzirasa He also selected connexins 34.7 and 35 because they are expected to function similarly in humans. Existing atlases of human gene expression profiles could identify which cells to target.
“These gene expression patterns are like a GPS marker,” he explains, showing which cells do what. Viruses carrying the necessary genomic material could be injected into the bloodstream and then cross the blood-brain barrier, which could also be opened with focused ultrasound.
But brain editing in people is still a long way off and raises ethical questions. As a note Ithai Rabinowitch of the Hebrew University of Jerusalem, we don't yet know whether the brain would respond by creating new neural connections that could undo the effects of the engineered synapses. or even create other potentially negative paths.
Despite these unknowns, the research opens up an exciting path: for the first time, we can imagine therapies that do not simply compensate for chemical imbalances, but that literally rebuild the brain’s connections. No longer just drugs, but actual personalized “neurological engineering” interventions.
Are we at the dawn of a new era for psychiatry? It is too early to say, but artificial synapses undoubtedly represent one of the most promising frontiers in the fight against mental disorders.
Find the official research here: https://www.biorxiv.org/content/10.1101/2025.03.25.645291v1
