Dr. Robert Hevner is studying how neurons make connections.

RobertHevner_145x145Discovering a new treatment breakthrough for brain disorders like autism depends on a foundation of intricate details, such as how microscopic axons form connections in the brain.

Dr. Robert Hevner, a researcher at the Center for Integrative Brain Research at Seattle Children’s Research Institute, focuses on contributing important discoveries to the essential stockpile of knowledge he hopes will further the ultimate goal of neuroregeneration — regrowth and repair of neurons. Hevner uses mouse models to examine the role of specific proteins called transcription factors, which guide the development of a neuron's unique properties. These properties include things like the physical shape of the neuron cell, and more importantly, the connections it makes to other parts of the brain.

The ability of neurons to make connections is crucial. “There’s evidence that in autism the cerebral cortex axons don’t connect appropriately to other lobes of the brain,” says Hevner.

Honing in on factor TBR1

One recent discovery Hevner made was that the brains of the mice in his lab were exhibiting properties similar to what is seen in human autism. He was working with genetically altered “knockout” mice — mice in which a specific transcription factor called TBR1 had been removed. These mice developed defective connections and other neuronal properties in the frontal lobe, a region of the brain that, in people, influences communication and characteristics seen in autism such as repetitive behavior and limited interests.

Normally, people have strong connections from their frontal lobes to their temporal lobes and parietal lobes, especially. But in autism those connections are weaker — as they were in the brains of Hevner’s knocked out mice. “We think TBR1 is related to autism,” Hevner says, though he stresses that his findings were in mice and the significance they hold for humans isn’t yet known.

Developing the technology needed to further research

Technology will play a crucial role in the discovery of even more cellular-level processes in mouse brains that could shed light on autism and other human brain disorders. Hevner and his colleagues joined forces with a private company and developed an enhancement to the Two Photon microscope in their lab at the research institute by splitting the scope’s laser beam. Says Hevner, “Now it’s like we have two microscopes, both driven by the same laser, and we can compare a normal brain and a ‘knockout’ brain, imaged at the same time under the same conditions.”