Researchers discover mechanism guiding wiring of complex neural circuits in brain

Weill Cornell Medical College researchers have uncovered a mechanism that guides the complex wiring of neural circuits in a developing brain – opening up possibilities of gaining insights not previously available, into faulty circuits that could lead to a range of brain disorders from autism to mental retardation.

Researchers describe in the journal Cell, for the first time, that faulty wiring occured when RNA molecules embedded in a growing axon were not degraded after they gave instructions that helped steer the nerve cell.

So, for instance, if the signal telling the axon to turn, that was to disappear after the turn was made, remained active, it would interfere with new signals meant to guide the axon in other directions.

According to scientists, there might be a way to use this new knowledge to fix the circuits.

According to Dr Samie Jaffry, a professor in the Department of Pharmacology and the study's senior author, understanding the basis of brain miswiring could help scientists come up with new therapies and strategies to correct the problem.

He added, the brain was quite 'plastic' and changeable in the very young, and if it was known why circuits were miswired, it might be possible to correct those pathways, allowing the brain to build new, functional wiring.

Epilepsy, autism, schizophrenia, mental retardation and spasticity and movement disorders, are some of the disorders associated with faulty neuronal circuits.

In the study, researchers investigated neurons that traveled up the spinal cord into the brain.

According to Dr Jaffrey, it was very critical that axons were precisely positioned in the spinal cord and if they were improperly positioned, they would form the wrong connections, which could lead to signals being sent to the wrong target cells in the brain.

The team found that RNA molecules embedded in the growth cone were responsible for instructing the axon to move left or right, up or down. These RNAs are translated in growth cones to produce antenna-like proteins that steer the axon like a self-guided missile.

As a circuit was in the process of being built, RNAs in the neuron`s growth cones were mostly silent. He added, the team found that specific RNAs only read at precise stages in order to produce the right protein needed to steer the axon at the right time. He said, after the protein was produced, the team saw that the RNA instruction was degraded and disappeared.

According to Dr Dilek Colak, a postdoctoral associate in Dr Jaffrey`s laboratory, the research finding answered a long-standing puzzle in the quest to understand brain wiring.