Brain's Inner Workings Revealed In Two New Nature Papers
April 3, 2014

BRAIN Initiative Anniversary Marked With Studies On Prenatal Development, Mouse Neural Network

redOrbit Staff & Wire Reports - Your Universe Online

On the one-year anniversary of the formation of the BRAIN Initiative, researchers from the Allen Institute for Brain Science announced the publication of two new scientific papers: one detailing the creation of a high-resolution blueprint of a prenatal human mind, and another showing the wiring of a mouse brain.

The 10 year, $100 million BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative was launched on April 2, 2012 with the goal of spurring on research exploring the deepest, innermost workings of the organ – especially in the fields of neurology, gray matter activity and diseases that impact the brain.

The first of the two studies published Wednesday used data from the BrainSpan Atlas of the Developing Human Brain – a project seeking to create a map of the set of RNA molecules known as the transcriptome throughout the course of a person’s development – to discover where genes within the central nervous system organ are activated in mid-pregnancy.

The study authors also set out to discover what genetic problems arise during brain development that leads to autism, using the data to examine several genes that had been linked to the condition in previous studies. They found that genes associated with newly generated excitatory neurons in the cortex could be linked to autism.

Furthermore, they set out to determine what makes the human brain unique, discovering several regions of the genome that featured strikingly different sequences when compared to other species. The genes that make people distinct were reportedly discovered in the frontal cortex, as well as inhibitory GABAergic interneurons and neurons found in the transient subplate zone – a region which plays a vital role during early circuit formation.

“Knowing where a gene is expressed in the brain can provide powerful clues about what its role is,” said Allen Institute investigator Ed Lein. “This atlas gives a comprehensive view of which genes are on and off in which specific nuclei and cell types while the brain is developing during pregnancy. This means that we have a blueprint for human development.”

Lein added that the atlas also provides “an understanding of the crucial pieces necessary for the brain to form in a normal, healthy way, and a powerful way to investigate what goes wrong in disease,” and that the study is “a terrific example of the potential for public-private partnerships to accelerate progress in neuroscience.”

In the second paper, a team of Allen Institute researchers revealed a mouse connectome. A connectome, explained Sharon Begley of Reuters, is a “map” or “wiring diagram” that shows how the millions of neurons in a rodent’s brain connect to thousands of others through white matter or axons in order to form functional circuits and allow different regions of the brain to communicate.

Lead investigator Hongkui Zeng and her colleagues used some of the same techniques to create the mouse connectome that would be required to create one for the human brain. They injected viruses into specific locations of living mouse brains, and those pathogens created a special glowing protein that diffuses throughout the neurons and axons.

Thanks to those fluorescent green proteins, the researchers were able to examine the mouse brains under a microscope and were able to locate all but 18 of the 295 distinct structures that made up the creature’s neural network. Begley said that those structures that were missing from the network were extremely small, located near the bottom of the brain and hard to expose to the virus.

“The map revealed several surprises about brain wiring,” she added, noting that Zeng told her that connections that stayed on just one side of the brain appeared to be stronger. In addition, there was a tremendous amount of variation in the strength of the neural network, which the researchers believe could be a trait of the network’s organizational system that allows for higher information processing capacity.

“Understanding how the brain is wired is among the most crucial steps to understanding how the brain encodes information,” Zeng explained. “The Allen Mouse Brain Connectivity Atlas is a standardized, quantitative, and comprehensive resource that will stimulate exciting investigations around the entire neuroscience community, and from which we have already gleaned unprecedented details into how structures are connected inside the brain.”