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Researchers Hongkui Zeng, Julie Harris and Hannah Choi check out a brain connectivity image at the Allen Institute for Brain Science. (Allen Institute Photo)

Researchers at Seattle’s Allen Institute say a new and improved map of the mouse brain reveals not only how different regions are connected, but how those connections are ordered in a hierarchical way.

They add that the mapping techniques behind their study, which was published today by the journal Nature, could shed light on how diseases like Alzheimer’s, Parkinson’s or schizophrenia tangle up connections in the human brain.

The map produced by the study is technically known as a medium-scale “connectome.” It’s been variously compared to a wiring diagram, organizational chart or subway map for the brain. An initial version of the map was published five years ago — and at the time, it was hailed as a landmark for brain science.

Like that earlier version of the Allen Mouse Brain Connectivity Atlas, the newly published map was created by injecting glow-in-the-dark viruses into the brains of mice, and then tracking how brain impulses lit up different types of brain cells.

“In the previous map, we weren’t able to describe which pathways came from which cell,” Julie Harris, one of the study’s lead authors, told GeekWire. Harris is associate director of neuroanatomy at the Allen Institute for Brain Science, a division of the Allen Institute.

This time around, the team focused on connections between the brain’s cortex and the thalamus, which serves as a relay center for sensory input. Interactions between those areas of the brain are thought to play a role in cognition and memory — “the things we know can go awry with diseases like Alzheimer’s,” Harris said.

The raw data made it look as if everything was connected to everything, Harris said. But more detailed analysis brought the hierarchical “org chart” properties of those connections into sharper focus.

An artist’s rendering charts cortical and thalamic connections in the mouse brain. (Illustration by Benedicte Rossi for Allen Institute)

The regions of the cortex associated with sensory information, such as vision and smell, tended to be lower down on the hierarchy. The regions associated with higher-level functions, such as calling up a memory evoked by a familiar scent, tended to be higher up.

There were characteristic patterns for the connections moving up the hierarchy as opposed to those moving down, but those patterns weren’t always followed.

“This is not a simple hierarchy, like a one-way sequence of ascending steps,” study co-author Christof Koch, chief scientist and president of the Allen Institute for Brain Science, said in a news release. “The next step will be to look directly at how neurons pass information through their electrical activity to confirm that this pattern matters.”

This animated image shows axon pathways originating from five different types of neurons located across the cortical layers. Each neuron type is false-colored in the movie. (Allen Institute Image)

Harris emphasized that the new map, like the old map, laid out the org chart for a normal mouse brain. She and her colleagues are now analyzing how the patterns of connections might differ in mice that have been genetically engineered to develop the symptoms of Alzheimer’s disease.

Such an analysis could point to new methods for repairing the misconnections in diseased brains — and open up new frontiers for treating human patients.

Neuroscientists still have a long way to go to get a complete picture of the roughly 100 billion connections between the brain cells of a mouse, let alone the hundreds of trillions of connections in the human brain. But each improvement in mapping technology brings the workings of our brains into clearer focus.

“These connections are the primary way neurons communicate with each other,” said senior study author Hongkui Zeng, who is executive director of structured science at the Allen Institute for Brain Science. “The elaborate and complicated networks in the brain, their different pathways and subsystems, process everything we see, our movements, memories and feelings. Understanding the connectivity of the brain is fundamental for understanding how the brain works.”

This image shows a single section from a mouse brain. Neurons in one layer of the sensory cortex (the very dense yellow color on the right) were labeled with green fluorescence to trace all the pathways arising from these cells across the brain. When these axons reach their cortical targets, they form synaptic connections across the layers of the cortex with distinct patterns associated with the direction of information routing. (Allen Institute Image)

Harris, Koch and Zeng are among 41 authors of the paper published in Nature, “Hierarchical Organization of Cortical and Thalamic Activity.” Stefan Mihalas, associate investigator at the Allen Institute for Brain Science, is co-lead author along with Harris.

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