To understand certain developmental brain disorders, the process behind how the brain develops must be understood. Cognitive problems such as autism will only truly be unraveled when neuroscientists can pinpoint exactly what goes wrong and when.

A new study at Washington University School of Medicine in St. Louis looked at synapses, or connections between neurons, to see how synapse formation is controlled in the developmental brain. Synapses allow neurons to transfer information along pathways from one part of the brain to another, relaying messages and signals. 

The researchers specifically looked at the cerebellum, which is the part of the brain in the back of your head and is used primarily for regulating movement, coordination and "motor learning", or moving your muscles unconsciously. Some believe that impairment in the cerebellum's nerve cell wiring may be a factor in autism spectrum disorders.

The team of scientists saw that a complex of proteins called nucleosome remodeling and deacetylase (NuRD) plays a role in regulating construction of the connections between in the cerebellum. In turn, this construction affects the ability to control movements and learn coordination.

"Impairment of the wiring of nerve cells in the cerebellum may contribute to movement disorders as well as cognitive problems," says Azad Bonni, senior author of the study published in Neuron. Bonni and his colleagues blocked the NuRD protein complex to see what happens when its functional role in constructing the cerebellum is inhibited. They found that certain cells in this region, called granule cells, failed to make connections with other nerve cells, called Purkinje neurons. Without these connections, control of motor learning is impaired.

How does a protein complex regulate this construction of synapses? The study found that the complex controls the construction via DNA, but it also affects the way in which genes are accessed. Changing this access subsequently changes the activity levels of specific genes. If the genes are inaccessible, certain proteins cannot be made, hindering the building blocks of synaptic formation.

Additionally the researchers found that NuRD changes the tags on some of the proteins used to store DNA. This diminished the chance of some genes being used, and deactivates certain genes that control activity of other genes necessary for building the circuitry in the cerebellum. 

"This tells us that the NuRD complex is very influential-not only does it affect the activity of genes directly, it also controls other regulators of multiple genes," says Bonni.

The symptoms of autism spectrum disorder are seen early in a child's developmental period. Such symptoms display a range of impairments in social communication, interactions and behaviors. Some children with the disorder do not respond to social and emotional cues, and may display impaired coordination. 

There is no cure yet. Treating the disorder early, however, with the appropriate medical care and therapies, can reduce symptoms so children can grow and learn successfully. Understanding the underlying causes of the disorder at the early, developmental level is imperative to finding a cure.

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