Short-lived neural connections in the mouse brain help activate sensory circuits, permanently affecting a mouse’s sense of touch. Neuroscientists at Cold Spring Harbor Laboratory have discovered that a receptor protein called mGluR1 helps regulate when these temporary connections are made. Their findings may help reveal the origins of several neurodevelopmental disorders and new ways to treat them.
Not everything in the brain is meant to last. As our brains are assembled, trillions of neural connections must be built or destroyed at the right time and place. Otherwise, the seeds of diseases like autism can take root. Cold Spring Harbor Laboratory Assistant Professor Gabrielle Pouchelon studies how the brain is wired early in life. In doing so, she hopes to find the origins of various brain dysfunctions and new ways to treat them.
In a new study, Pouchelon and his team focus on a process known as pruning, which involves the brain removing unnecessary connections between neurons. Pruning long-lasting connections is relatively well-known. Pouchelon’s team focuses on special early connections that are severed to make way for long-lasting circuits in the mature brain. Although temporary, these early connections may play a critical role in shaping developing brain circuits.
Pouchelon’s lab has discovered that a receptor protein called mGluR1 helps regulate the timing of these temporary connections in the brains of mice. Her team found that without mGluR1, neural connections linger too long in the brain region that controls and processes touch through the whiskers. When the sensory circuitry doesn’t mature properly, the mice display atypical behaviors. For example, they don’t stand on their hind legs or sniff around 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 appears to be different than what has been described in adulthood,” Pouchelon says. “In the context of neurodevelopmental disorders, that means that when we try to target developmental defects, we might have a totally different therapeutic effect at different stages during development.”
Pouchelon’s team hopes their discovery will serve as a guide for designing future therapies to treat brain dysfunction early on. “The brain is a wonderful machine whose job is to adapt,” says Dimitri Dumontier, the postdoctoral researcher in Pouchelon’s lab who co-led this study. “So when you study neurodevelopmental disorders in adults or even adolescents, it’s difficult to identify which mechanisms are causing the symptoms. That’s why understanding the early milestones of brain development is key.”
The hope is that by figuring out exactly how the brain matures, scientists can rescue this process early. This could help prevent the symptoms of neurological disorders such as autism from appearing. After all, the world is hard enough to navigate. Pouchelon and Dumontier’s work could one day help make life easier for countless young people.