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Scientists have built the largest ever multi-species atlas of a brain region crucial for movement, emotion and decision-making, paving the way for potential breakthroughs for diseases such as Parkinson’s disease, bipolar disorder and autism.
Researchers have discovered a new cell type linked to schizophrenia, a potential gene therapy to reduce Parkinson’s tremors and changes in gene expression linked to aging.
This effort, involving hundreds of scientists from more than 50 institutions across nine countries, highlights how a combination of technological advances and international collaboration is opening new possibilities to combat destructive neurological problems.
The basal ganglia is the “big hub” of many brain diseases, said Evan Macosko, an associate professor at Harvard Medical School who worked on the research.
“We really need to have a clear understanding of how these different areas of the brain work if we’re going to try to repair them,” said Macosko, a senior fellow at the Broad Institute for biomedical Research. “We hope that this basic map that we have presented will be the model that many neuroscientists can rely on to help them understand this complex and important structure.”
The atlas uses data from humans, macaques, marmosets and mice, according to more than two dozen articles about the work published Thursday in the Cell Press family of journals. The researchers profiled 25.5 million cells, most from people, using cutting-edge analysis of their gene activity.
“Diseases are always specific to a cell type, so to understand what’s really going on in the brain, you need to have an accurate list of cell types and look at the expression of individual genes in each cell type,” said Hongkui Zeng, executive vice president and director of brain sciences at the Allen Institute, who also participated in the research.
Scientists have discovered how a rare type of nerve cell is linked to an increased risk of schizophrenia. This will allow researchers to focus future work on people with the same genetic disease signal.
A second study found that a modified version of an existing gene therapy for Parkinson’s disease was more effective at reducing tremors in animals, while being less invasive.
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Another strand of research has found that genetic changes in certain types of basal ganglia cells may play a role in autism. Another group of scientists showed how aging could be predicted from the genetic activity patterns of several cell types.
The research has provided an “essential road map” for a region of the brain without which “we can’t breathe, we can’t move, we can’t live”, said Frank Hirth, professor of evolutionary neuroscience at King’s College London. “This complex neural network coordinates involuntary and voluntary motor actions, motivated behaviors and decision-making, and is necessary for internal representations of embodiment and the sensory environment,” Hirth said. “You close your eyes and you can’t see, but you know where the door is to get out of the room. You think about Grandma’s heavenly crumble and you want to call to say I miss you.”
Other scientists not involved in the work praised its scale and scope, highlighting ways to develop it further. It would be crucial to see how the “molecular snapshots” matched the behavior of living cells, said Nina Rzechorzek, an MRC clinical research fellow at the University of Cambridge.
“The next step is to determine which molecular differences causally contribute to dysfunction, which reflect potentially reversible adaptations, and whether intervening in these processes improves brain health,” Rzechorzek said. “This requires functional experiments and independent mechanistic validation as well as increasingly sophisticated molecular reference maps.”
Gn Health
