Scientists have developed a protein that can temporarily turn specific brain connections on and off, by destroying the connections between individual neurons. Using this new tool, researchers may one day be able to develop new treatments for cognitive disorders that precisely target the faulty brain connections, rather than using risky medications that often produce an array of nasty side-effects.
A range of drugs that alter connectivity in the brain are currently available, including antidepressants like benzodiazapines. However, such medications tend to have quite a messy mode of action, targeting all the cells in a particular brain region rather than honing in on specific faulty neurons and connections.
Greater finesse is therefore required in order to safely treat neurological conditions, and researchers from the US and Canada believe they may now have the perfect instrument for doing so, in the form of a protein called GFE3. Detailing their work in the journal Nature Methods, the study authors describe how they synthesized the molecule by combining two other proteins that bind to a substance called gephyrin.
Gephyrin is present at the connections – or synapses – between inhibitory neurons in the brain, essentially holding them together and enabling these neurons to communicate by sending neurotransmitters to one another. When they do so, they produce a range of inhibitory effects, reducing activity in certain parts of the brain.
While this helps to regulate our cognitive function, the process can sometimes go wrong, leading to a number of neurological disorders.
Using a virus, the researchers were able to infect specific neurons in the brains of zebrafish and mice with sections of genetic code that caused them to generate GFE3. This led to an 80 percent reduction in gephyrin levels at the synapses formed by those neurons, preventing them from performing their inhibitory function.
In zebrafish, for instance, the protein silenced the inhibitory synapses that keep muscle movement under control, causing the fish to wildly thrash their tails around as their muscles spontaneously contracted.
By then removing this genetic code using another virus, the researchers were able to reverse this effect, with no lasting damage or alterations to the animals’ brains.
Summarizing this process in a statement, lead researcher Don Arnold explained that “rather than a cell deciding when a protein needs to be degraded, we sort of hijack the process.” In doing so, he says, “we can target and modulate the inhibitory synapses of specific cells without affecting other cells that have different functions.”