'Timing is everything' in ensuring healthy brain development

Work published today shows that brain cells need to create links early on in their existence, when they are physically close together, to ensure successful connections across the brain throughout life.

In people, these long-distance connections enable the left and right side of the brain to communicate and integrate different kinds of information such as sound and vision. A change in the number of these connections has been found in many developmental brain disorders including autism, epilepsy and schizophrenia.

The Newcastle University researchers Dr Marcus Kaiser and Mrs Sreedevi Varier carried out a sophisticated computer analysis relating birth-time associated data to connectivity patterns of nerve cells in the roundworm, Caenorhabditis elegans. They demonstrated that when two nerve cells develop close together, they form a connection which then stretches out when the two nerve cells move apart as the organism grows. This creates a link across the brain known as a long-distance connection.

Publishing today in PLoS Computational Biology, the researchers have demonstrated for the first time that this is the most frequent successful mechanism by which long distance connections are made.

Dr Marcus Kaiser, at Newcastle University, says: "You can draw parallels with childhood friendships carrying on into adulthood. For example, two children living close to each other could become friends through common activities like school or playing at the park. The friendship can last even if one of them moves further away, while, beginning a lasting friendship with someone already far away, is much more difficult."

Mrs Sreedevi Varier adds: "Although it's too early for this research to have direct clinical applications, it adds to our understanding of the structural changes in the brain and raises some interesting questions as to how these connections can become faulty. In further studying this mechanism, we may eventually contribute towards insights into the diagnosis and possibly the treatment of patients with epilepsy and autism."

It has long been understood that the first connections in the brain created in the early days of development can be formed over long distances using guidance signals to direct nerve fibres to their correct positions – known as axonal guidance. Subsequently, other connections can follow those pioneer fibres to a target location creating connections between distant parts of the brain. Through these long-distance connections different kinds of information, such as sound and vision, can be integrated.

This EPSRC-funded research showed that most neurons are able to create a connection early on in their development when they were physically close together, potentially giving them more time to host and establish connections. These developed into a long-distance connection, the two cells pulling apart as the organism grows larger.

Studying the connections in the neuronal network of the roundworm Caenorhabditis elegans the Newcastle scientists - who are also affiliated with Seoul National University, Korea - found that most neurons with a long-distance connection had developed in this way.