Study Finds That Autism Could Begin Very Early In Brain Development

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A recent study suggests that too many connections in the brain could be partly responsible for the symptoms of autism, including communication deficits and unusual talents. The new study by researchers at the University of Maryland found that the excessive connections begins early in mammalian development, when major neurons in the region of the brain known as the cerebral cortex begin to form their first circuits.

Researchers believe that the findings of the study could lead to a better understanding of autism in humans by determining where and when autism-related neural defects first emerge in mice, including possible early intervention strategies.

"Our work suggests that the neural pathology of autism manifests in the earliest cortical circuits, formed by a cell type called subplate neurons," UMD Biology Professor and senior author of the study, Patrick Kanold said. He added that nobody has looked at the developing circuits this early and in the context of autism before.

Subplate neurons form the first connections in the developing cerebral cortex, which is the outer part of the mammalian brain that controls perception, memory, language and abstract reasoning in humans. As the brain develops, the interconnected subplate neurons build a network of scaffolding thought to support other neurons that grow later in development.

A former postdoctoral researcher at UMD and lead author of the study, Daniel Nagode noted that the cortex is a very important region in the adult human brain that undergoes a complex, multi-stage development process, and because their findings implicate the early stages of cortex circuit formation in a mouse model, they suggest that the pathological changes that causes autism might start before birth in humans, According to Medical Express.

In order to study the relationship between subplate neuron development in mice and autism and, the  researchers started with an established mouse model of autism, which involves dosing the embryo of mouse with valproic acid (VPA) and injecting the drug into the mother mouse on the twelfth day of their gestation period.

The drug has been linked to autism in humans and is also known to induce cognitive and behavioral abnormalities in mice, including an abnormal reduction in noise making as normal newborn pups do. The study authors utilized a technique known as laser scanning photostimulation to monitor the connections between individual subplate neuron cells in the brains of the mouse pups.

They found that the VPA-dosed mice showed some patches of "hyperconnected" subplate neurons in the first week after birth, in contrast with the control mouse pups that were administered plain saline solution. The researchers report that they displayed normal connections throughout their cortical tissue.

The patches of hyper-connected subplate neurons became widespread in the VPA-dosed pups compared to the control mouse pups just ten days after birth.  A thicket of hyperconnected subplate neurons in the developing cortex could result in permanent hyperconnections as the subplate neurons have already laid the foundation for cortical development in all mammalian brains, according to Science Daily.

The researchers said that hyper-connections in the developing cortex could result in the neural pathologies observed in human autism, if the same dynamic plays out in human brains. The critical window of time when subplate neurons develop is very short in both mice and humans.

Subplate neuron development in mice takes place mostly after birth and it eventually dies and disappears when their job is complete with other neural circuits taking their place. But the first subplate neuron connections form in the second trimester in humans, with most of them disappearing before a person is born. The researchers published their findings Jan. 31, 2017 in the journal Cell Reports.