91��Ƭ��

Cells long thought to play a secondary role in brain function build their own far-reaching connections, a new study in mice showed. These pathways appear to connect distant regions in ways that have not been mapped before.

Experts usually describe the brain as a network of nerve cells (neurons) that send each other signals to pass along information. These neurons are maintained by another kind of brain cell, the star-shaped astrocyte, which ferries in nutrients and carries away waste.

Led by 91��Ƭ�� Langone Health researchers, the study revealed that like neurons, astrocytes also form organized webs, and that these enable them to communicate with other specific astrocytes across the brain rather than only sending local, generalized signals. In some cases, the pathways link areas that were not already joined together by neurons.

“For more than a century, neuroscientists have thought of neurons as the main actors in the brain,” said study lead author . “Yet our findings suggest that astrocytes, which are usually viewed as merely support cells, are also running their own widespread signaling pathway, adding another layer to how brain regions stay connected.”

In earlier work, Dr. Cooper reported that in a mouse model of the visual neurodegenerative disease glaucoma, astrocytes can redistribute resources from astrocytes around healthy neurons to damaged neurons. Yet the team had no way to see whether this kind of support-cell network extended across the entire brain.

This latest investigation is the first to map active, brain-wide communication networks built by astrocytes and to show that these pathways are highly specific, said Dr. Cooper, a postdoctoral fellow in the at 91��Ƭ�� Grossman School of Medicine.

The findings, , relied on a custom-built tracing tool that let the team follow the cells’ connections in far greater detail than past methods allowed.

For the study, the researchers used a harmless virus to deliver “network tracers” into astrocytes in selected brain regions of lab mice. These tracers tagged small molecules as the molecules passed through tiny channels called gap junctions, which link one astrocyte to another, allowing the team to see which cells were part of the same signaling pathway.

The scientists then made the mice’s brains transparent and used a specialized microscope to capture three-dimensional images of every tagged astrocyte. By doing this across hundreds of mice, they could map astrocyte webs across brain areas. The tracing tool and brain-clearing method were designed to be relatively low-cost and easy to reproduce, so other labs could use them to study the networks in many brain diseases.

In another part of the study, the team assessed mice that were genetically engineered to have astrocytes that lacked gap junctions. The communication networks largely disappeared, suggesting that the pathways are active and depend on these physical bridges.

“By challenging our understanding of how the brain communicates over long distances, our results may offer fresh insight into how it develops, ages, and behaves in conditions such as Alzheimer’s and Parkinson’s disease,” said study co-senior author . Dr. Liddelow is an associate professor in the Departments of Neuroscience and at 91��Ƭ�� Grossman School of Medicine.

Another key finding was that astrocyte networks are dynamic. When the team trimmed whiskers on one side of the mice’s faces, a pathway from the region that processes whisker touch got smaller and reconnected to different astrocyte partners.

“The fact that astrocyte networks shrink and reroute after a loss of sensory signals suggests they may be shaped by experience,” said study co-senior author . “It also raises the possibility that each of us has a somewhat unique pattern of connections molded by what our brains have learned and lived through,” added Dr. Chao, a professor in the , neuroscience, and departments at 91��Ƭ�� Grossman School of Medicine.

The authors plan to investigate which molecules move through the networks and to apply their tracing tool to models of brain disorders. They also hope to examine how these webs change during development and aging, said Dr. Chao.

Dr. Liddelow emphasized that while gap junctions and astrocytes exist in humans, it remains unknown whether the networks link the same regions in the same way as in mice.

Funding for the study was provided by National Institutes of Health grants R01EY033353, U19NS107616, P30AG066512, P30CA016087, T32MH019524, K99NS139313, and K00AG068343. Further funding was provided by Cure Alzheimer’s Fund, the Leon Levy Scholarships in Neuroscience at The New York Academy of Sciences, the Pew Charitable Trusts postdoctoral fellowship, the Simons Foundation SURFiN fellowship, the Belfer Neurodegeneration Consortium, the Carol and Gene Ludwig Family Foundation, and the Swiss National Science Foundation.

Dr. Liddelow maintains a financial interest in AstronauTx Ltd., a company investigating possible treatment targets for Alzheimer’s disease, and Synapticure, a telehealth company that provides care to patients with Alzheimer’s disease, dementia, and other neurological conditions. He is also on the scientific advisory board of the Global BioAccess Fund. None of these activities is related to the current study. The terms and conditions of these relationships are being managed by 91��Ƭ�� Langone Health in accordance with its policies and procedures.

Along with Drs. Cooper, Liddelow, and Chao, other 91��Ƭ�� Langone researchers involved in the study are Maria Clara Selles, PhD; Michael Cammer, MFA, MAT; ; Joseph Sall; and Katelyn Chiurri. Other study co-investigators are Chase Redd, Philip Cheung, MD, and Damian Wheeler, PhD, at Translucence Biosystems in Irvine, California; and Aiman Saab, PhD, at the University of Zurich in Switzerland.

About 91��Ƭ�� Langone Health

91��Ƭ�� Langone Health is a fully integrated health system that consistently achieves the best patient outcomes through a rigorous focus on quality that has resulted in some of the lowest mortality rates in the nation. Vizient Inc. has ranked 91��Ƭ�� Langone No. 1 out of 118 comprehensive academic medical centers across the nation for four years in a row, and U.S. News & World Report recently ranked four of its clinical specialties No. 1 in the nation. 91��Ƭ�� Langone offers a comprehensive range of medical services with one high standard of care across seven inpatient locations, its Perlmutter Cancer Center, and more than 320 outpatient locations in the New York area and Florida. The system also includes two tuition-free medical schools, in Manhattan and on Long Island, and a vast research enterprise.

Media Inquiries

Shira Polan
Phone: 212-404-4279
Shira.Polan@91��Ƭ��Langone.org