Study reveals mGluR1’s role in pruning early neuronal connections

Not everything is in the brain to last. As our brain comes together, trillions of neural connections must be made or broken at the right time and place. Otherwise, the seeds of disorders like autism can take root. Cold Spring Harbor Laboratory assistant professor Gabrielle Pouchelon studies how the brain is wired early in life. In this way, he hopes to find the origin of various brain malfunctions and new ways to treat them.

In a new study, Pouchelon and her team accept a process known as pruning. This happens when the brain removes unnecessary connections between neurons. Pruning long-running links is relatively well known. Pouchelon’s team focuses on specific early connections that are severed to make room for long-lasting circuits in the mature brain. Although temporary, these early connections may play a critical role in shaping the brain’s developing circuits.

Pouchelon’s lab has now discovered that a receptor protein called mGluR1 helps regulate the timing of these temporary connections in the mouse brain. Her team found that without mGluR1, neural connections stick around for too long in the area of ​​the brain that controls and processes touch through whiskers. When the sensory circuit fails to mature properly, mice exhibit atypical behaviors. For example, they don’t stand on their hind legs and sniff like other mice do.

Importantly, the team notes that this critical step in circuit development occurs during the first week after birth. “The way the receptor works seems to be different from what has been described in adulthood,” says Pouchelon. “In the context of neurodevelopmental disorders, this means that when we try to target developmental defects, we could have a completely different therapeutic effect at different stages during development.”

Pouchelon’s team hopes their discovery can serve as a guide for designing future treatments to treat brain dysfunction early. “The brain is a wonderful machine, whose job it is to adapt,” says Dimitri Dumontier, the postdoctoral fellow in Pouchelon’s lab who co-led this study. “So when you study neurodevelopmental disorders in adults or even adolescents, it’s difficult to determine which mechanisms are causing the symptoms. So understanding the early milestones of brain development is key.”

The hope is that by discovering exactly how the brain matures, scientists can rescue this process early. This could help prevent the onset of symptoms of neurological disorders such as autism. Besides, the world is hard enough to navigate as it is. Pouchelon and Dumontier’s work could one day help make the lives of countless young people easier.