Australian scientists map mouse brains in greatest detail yet

Hopes for a cure for many brain diseases may rest on the humble mouse, now that scientists can map the rodents’ brains more thoroughly than ever before.

Researchers at The University of Queensland’s Centre for Advanced Imaging (CAI) and Curtin University have created the most detailed atlas of the mouse brain, a development that is helping in the fight against brain disease.

This new tool will allow researchers to map what parts of the brain are affected in mouse models of brain disease – such as brain cancer, Parkinson’s disease and Alzheimers disease, which affect nearly 1 in 6 of the world’s population.

Lead author, Dr Jeremy Ullmann said that the new brain atlas provided a fundamental tool for the neuroscience community.

“The mouse is now the most widely used animal model for neuroscience research and magnetic resonance imaging (MRI) is fundamental to investigating changes in the brain,” Dr Ullman said.

“Our atlas is already much in demand internationally because it allows researchers to use MRI to automatically map brain structures.”

The atlas was created in the laboratory of Professor David Reutens, CAI Director.

“In making these world-first maps, we had the advantage of using the most powerful MRI scanners in the Southern Hemisphere, backed up by leaders in digital image analysis, resulting in remarkably clear images of the brain,” Professor Reutens said.

The project’s lead neuroanatomist, Professor Charles Watson from Curtin University, believes that the study will open the door to accurate analysis of gene targeting in the mouse brain.

“The invention of gene targeting in the mouse has made this species the centrepiece of studies on models of human brain disease. MRI allows researchers to follow changes in the brain over time in the same animals,” Professor Watson said.

The atlas was recently described in an article published in the journal NeuroImage.

Pig brain models provide insights into human cognitive development

A mutual curiosity about patterns of growth and development in pig brains has brought two University of Illinois research groups together. Animal scientists Rod Johnson and Ryan Dilger have developed a model of the pig brain that they plan to use to answer important questions about human brain development.

“It is important to characterize the normal brain growth trajectory from the neonatal period to sexual maturity,” said Johnson.

“Until we know how the brain grows, we don’t know what is going to change,” added Dilger.

In cooperation with the Beckman Institute, they performed MRI scans on the brains of 16 piglets, starting at the age of 2 weeks, then at 4 weeks, and then at 4-week intervals up to 24 weeks.

“We have world-class people at the Beckman Institute who are pushing and developing the next generation of neuroimaging technology, so we’re able to connect with them and take advantage of their expertise,” said Johnson.

Matt Conrad, a student in Johnson’s lab, used three-dimensional visualization software on over 200 images to manually segment each region on three planes. The software put the information together into a three-dimensional image of the pig brain. This is used to determine the volume of the different structures.

When the piglets were at Beckman for their imaging sessions, Dilger performed other tests, including diffusion tensor imaging (DTI), which shows how neural tracks develop, allowing the exploration of brain complexity and of how neurons form. It was also possible to measure neurochemicals, including creatine and acetylcholine, in the brain, which provides a unique insight into brain metabolism.

The end result of this work is what they call the deformable pig brain atlas.

“We are taking 16 pigs and averaging them, so it’s more representative of all pigs,” said Dilger. “You can then apply it to any individual pig to see how it’s different.”

“It’s called a deformable brain atlas because the software takes information from an individual and deforms it until it fits the template, and then you know how much it had to be deformed to fit,” Johnson explained. “So from that, you can tell whether a brain region is larger or smaller compared to the average.”

Johnson and Dilger said that the goal is to develop a tool for pigs that is equivalent to what is available for the mouse brain and make it publicly available. But they don’t want to stop with tool development.

“We want to use this to address important questions,” Johnson said.

One research direction being pursued in Johnson’s lab is to induce viral pneumonia in piglets at the point in the post-natal period when the brain is undergoing massive growth to see how it alters brain growth and development. They are also looking at effects of prenatal infections in the mother to see if that alters the trajectory of normal brain growth in the offspring. The risk for behavioral disorders and reduced stress resilience is increased by pre- and post-natal infection, but the developmental origins are poorly understood.

Dilger’s group is interested in the effects of early-life nutrition on the brain. They are looking at the effects of specific fatty acids as primary structural components of the human brain and cerebral cortex, and at choline, a nutrient that is important for DNA production and normal functioning of neurons.

“Choline deficiency has been tied to cognitive deficits in the mouse and human, and we’re developing a pig model to study the direct effects choline deficiency has on brain structure and function,” Dilger said. “Many women of child-bearing age may not be receiving enough choline in their diets, and recent evidence suggests this may ultimately affect learning and memory ability in their children. Luckily, choline can be found in common foods, especially eggs and meat products, including bacon.”

First extensive analysis of Allen Human Brain Atlas published in Nature has implications for basic understanding of the human brain and for medicine

Scientists at the Allen Institute for Brain Science reported in the latest issue of the journal Nature that human brains share a consistent genetic blueprint and possess enormous biochemical complexity. The findings stem from the first deep and large-scale analysis of the vast data set publicly available in the Allen Human Brain Atlas.

The results of this study are based on extensive analysis of the Allen Human Brain Atlas, specifically the detailed all-genes, all-structures survey of genes at work throughout the human brain. This dataset profiles 400 to 500 distinct brain areas per hemisphere using microarray technology and comprises more than 100 million gene expression measurements covering three individual human brains to date. Among other findings, these data show that 84% of all genes are expressed somewhere in the human brain and in patterns that are substantially similar from one brain to the next.

"This study demonstrates the value of a global analysis of gene expression throughout the entire brain and has implications for understanding brain function, development, evolution and disease," said Ed Lein, Ph.D., Associate Investigator at the Allen Institute for Brain Science and co-lead author on the paper. "These results only scratch the surface of what can be learned from this immense data set. We look forward to seeing what others will discover."