The GFE3 protein may help researchers map the brain's connections and better understand how inhibitory synapses modulate brain function, according to Don B Arnold from University of Southern California in the US. It also may enable them to control neural activity and lead to advancements in research for diseases or conditions ranging from schizophrenia to cocaine addiction, he said.
The new tool is a protein that carries a death sentence for synaptic proteins in specific cells. The protein can be encoded in animal genomes to effectively switch off their inhibitory synapses - connections between neurons - increasing their electrical activity, researchers said.
"GFE3 harnesses a little known and remarkable property of proteins within the brain," said Arnold. The protein takes advantage of an intrinsic process - the brain's cycle of degrading and replacing proteins. Most brain proteins last only a couple of days before they are actively degraded and replaced by new proteins, researchers said. GFE3 targets proteins that hold inhibitory synapses together to this degradation system and as a result, the synapses fall apart, they said. "Rather than a cell deciding when a protein needs to be degraded, we sort of hijack the process," said Arnold.
For the study, scientists studied the protein's effect in both mice and zebrafish. They found that GFE3 protein triggered the neurons on the two sides of the spine to work in opposition, generating uncoordinated movements.
Previously, drugs could be used to inhibit inhibitory synapses in the brain, for instance benzodiazapines, which treat anxiety, insomnia or seizures, researchers said. But the drugs inhibit all the cells in a particular area, not just the neurons that are the intended target.
"Unfortunately, cells that have very different, even opposite functions tend to be right next to each other in the brain," said Arnold. "Thus, pharmacological experiments are especially difficult to interpret. By encoding GFE3 within the genome, we can target and modulate the inhibitory synapses of specific cells without affecting other cells that have different functions," he said.
The findings were published in the journal, Nature Methods.
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