Understanding the Origins of Brain Disorders Through Neural Pruning

The brain does not retain information indefinitely. Trillions of neurons must be assembled or eliminated at precise times and locations as human brains develop. If this process goes awry, conditions such as autism may arise.

Associate Professor Gabrielle Pouchelon of Cold Spring Harbor Laboratory has been investigating the early wiring of the brain. Through this research, Pouchelon aims to uncover the causes of various brain disorders and develop innovative approaches to their management.

Pouchelon and colleagues focus on the pruning process in a recent study. This is the process by which the brain prunes unneeded connections among neurons. It is fairly common knowledge that long-lasting connections should be pruned.

The research of Pouchelon's group focuses on unique early connections that are severed to create durable circuits in the developed brain. These early connections may be crucial in forming developing brain circuits, despite their transience.

Recently, Pouchelon's lab has found that the timing of these transient connections in the mouse brain is regulated by a receptor protein called mGluR1. Her team discovered that in the brain region responsible for controlling and processing touch via the whiskers, neural connections persist excessively long in the absence of mGluR1. The mice show unusual behaviors when the sensory circuit does not develop appropriately. Unlike other mice, they do not, for instance, stand on their hind legs and sniff around.

Crucially, the group observes that the first week following birth is when this crucial stage of circuit development takes place.

The way the receptor works seems to be different than what has been described in adulthood. In the context of neurodevelopmental disorders, that means when we try to target developmental defects, we could have a totally different therapeutic effect at different stages during development.”

Gabrielle Pouchelon, Associate Professor, Cold Spring Harbor Laboratory

Pouchelon’s team hopes their discovery may serve as a guide for designing future therapeutics to treat brain dysfunction early.

The brain is a wonderful machine whose job is to adapt. So, when you study neurodevelopmental disorders in adults or even teenagers, it is difficult to identify which mechanisms are causing the symptoms. That is why understanding early milestones of brain development is key.”

Dimitri Dumontier, Cold Spring Harbor Laboratory

It is hoped that by understanding the precise process of brain maturation, scientists will be able to stop it early. This may help delay the onset of symptoms associated with neurological conditions like autism.