How does glial organization compare across brain regions and species?

Background: Neurons have dominated neuroscience research for decades, but a growing body of evidence suggests that a group of non-neuronal brain cells called glia may play an equal or greater role in shaping brain health and disease. The human brain contains as many glial cells as it does neurons, yet we know far less about their organization and how they might contribute to the unique functions of each brain area.

New findings: Scientists at the Salk Institute, led by Terrence Sejnowski, PhD, and Shyam Srinivasan, PhD, compared glial organization across multiple brain regions and mammalian species, revealing new insights into the role of glia in shaping brain circuit function.

In the study, published in PNAS Nexus on October 16, 2025, the researchers surveyed available samples and datasets from human, rodent, and other mammalian tissues, comparing four brain regions with distinct functions: the anterior and posterior piriform cortex (smell and emotional processing), the entorhinal cortex (memory, spatial navigation, and time perception), and the cerebellum (movement, coordination, and learning).

Using histology and single-cell RNA sequencing, the researchers measured the density and ratio of each of the three major glial cell types—microglia, oligodendrocytes, and astrocytes. Their results showed that both glial density and the relative proportion of each cell type differed significantly across the four brain regions, suggesting that glial organization is not uniform across the brain but rather circuit-dependent.

Importantly, these regional specificities were conserved across mammals, and the ratio of glia to neurons also scaled consistently across species. These findings reveal a tight coupling between glia and neurons that is brain-region specific and evolutionarily conserved.

Why this is important: Until recently, glia were viewed as the brain’s support cells—existing to keep neurons healthy but not playing an active role in cognition. Previous studies comparing glial properties in the mammalian neocortex suggested that their organization was relatively uniform across the brain. Here, Salk scientists shift that perspective by assessing four new brain regions and showing that each area’s distinct circuitry is supported by a unique glial organization that has been evolutionarily conserved across species. The results also suggest that glia may sometimes be a better marker of regional identity than neurons, particularly outside the neocortex.  

Salk’s latest study provides further evidence for glia’s previously unappreciated role in shaping brain circuitry and cognition. The findings indicate that future studies should examine the role of glia as much as neurons in contributing to brain dysfunction and neurodegenerative disorders such as Alzheimer's disease.

Other authors: Other authors include Antonio Pinto-Duarte and Katharine Bogue of Salk.

Funding: The work was supported by the Kavli Institute, the National Institutes of Health (DC017695), the National Science Foundation’s Next Generation Networks for Neuroscience (NeuroNex).

About the Salk Institute for Biological Studies:

Unlocking the secrets of life itself is the driving force behind the Salk Institute. Our team of world-class, award-winning scientists pushes the boundaries of knowledge in areas such as neuroscience, cancer research, aging, immunobiology, plant biology, computational biology, and more. Founded by Jonas Salk, developer of the first safe and effective polio vaccine, the Institute is an independent, nonprofit research organization and architectural landmark: small by choice, intimate by nature, and fearless in the face of any challenge. Learn more at www.salk.edu.