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Researchers identify autism-linked receptor that initiates synaptic pruning

Synaptic pruning is a little like sleep. We know both processes are important to healthy brain function, but we don’t know exactly how they happen, nor how to reliably treat problems in the system. Disruptions in the delicate process of synaptic pruning are associated with disorders like schizophrenia and autism, which makes them hot topics for neuroscience research.

“The number of brain connections decreases by half after puberty,” explains Sheryl Smith, Ph.D., professor of physiology at SUNY Downstate Medical Center. Problems with that process can be disastrous. Now researchers led by Dr. Smith and colleagues from SUNY Downstate reported in eLife that they’ve isolated the process which initiates synaptic pruning at puberty, offering a new angle for both research and medicine.

Adolescent synaptic pruning is important for normal learning and memory function in adulthood. Dr. Smith explains, “Working with a mouse model we have shown that, at puberty, there is an increase in inhibitory GABA receptors, which are targets for brain chemicals that quiet down nerve cells.” These GABA receptors are responsible for initiating synaptic pruning in the mouse hippocampus once the mouse reaches the appropriate age.

Expressing the GABA receptor proteins actually reduces overall brain activity, because the GABA receptors are inhibitory — but that’s not the whole story. Dr. Smith and colleagues report that GABA receptors also reduce levels of a protein called kalirin-7, which stabilizes the internal scaffolding of dendritic spines to maintain their structure. Mice that don’t express the GABA receptors also don’t undergo synaptic pruning. In that disordered state, Dr. Smith adds, mice can learn spatial locations so that they have a limited sense of place, but they can’t relearn new locations after the initial learning. This suggests that the quelling influence of the GABA receptor serves to remove irrelevant synaptic connections.

Recent medical research found too many synapses in the temporal lobes of autistic children, suggesting that they don’t go through synaptic pruning as expected. Other research found that people with schizophrenia tend to have fewer neural connections than those who don’t have the condition.

Findings like these suggest that GABA receptors could be a target for new drugs or treatments aimed at properly regulating synaptic pruning. But things that muck about with receptors in the brain can have shocking and severe consequences, and while we have found one immunosuppressant drug that can decrease synaptic pruning, it has serious side effects. New treatments targeting GABA receptors will have to be exhaustively researched and carefully targeted if they’re going to avoid the Lovecraftian horror of genetic engineering gone wrong.

Now read: What is gene therapy?

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