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Most neuroscience research carried out up to date has primarily focused on neurons, the most renowned type of cell in the human brain. As a result, the unique functions of other brain cell types are less understood and have often been entirely overlooked. Researchers at Instituto Cajal (CSIC), the Autonomous University of Madrid and Institute de Salud Carlos III recently carried out a study aimed at better understanding the contributions of astrocytes, a class of star-shaped glial cells found in the brain and spinal cord, to key mental functions.
Their findings, published in Nature Neuroscience , unveiled the existence of astrocytic ensembles, specialized astrocyte subsets that appear to be active during reward-driven behaviors. "It is known that astrocytes are a heterogeneous cell type in their molecular and gene expression signatures, morphology and origin," Marta Navarrete, senior author of the paper, told Medical Xpress. "However, unlike neurons, so far, nothing was known about the functional diversity of astrocytes.
In this work, we wanted to study if and how astrocytes can be distinguished based on the roles that they play within the different circuits that they are part of." To closely examine the activity and contributions of astrocytes, the researchers used a new experimental tool that they developed, dubbed AstroLight. This promising tool allowed them to map the organization of this less-studied class of cells while also manipulating their activity using light.
"We adapted a tool originally designed for neurons, which is not ideal for them since their activity primarily depends on action potentials rather than calcium ion fluctuations," explained Navarrete. "However, because astrocytic activity is largely driven by calcium dynamics, this tool is particularly well-suited for studying astrocytes." The researchers used the AstroLight tool to label and manipulate astrocytes in the brains of mice as they were completing a behavioral task.
Their findings gathered new valuable insights into the specialized role of this unique class of glial cells in motivation and cue-driven behaviors. "Using the new tool we adapted, we translated astrocytic calcium signals into light-dependent gene expression, enabling us to identify and manipulate an active astrocytic ensemble in the posterior-ventral region of the Nucleus Accumbens (NAc) in mice," said Navarrete. "Our findings demonstrate that learning cue-reward associations involves increased astrocytic activity in the NAc and that this activity is not uniform but rather confined to a specific, sparsely distributed subset of astrocytes—an 'astrocytic ensemble.
' We show that direct optogenetic activation of this ensemble is sufficient to drive reward-seeking behavior, whereas activating the entire astrocyte population is not." The new findings gathered by Navarrete and her colleagues could have important implications for the study of astrocytes and their role in neural circuits , as they appear to contradict long-standing assumptions regarding the organization of these cells. Although astrocytes were traditionally viewed as a homogeneous cell population, the researchers showed that they could, in fact, operate in specialized groups, thus fine-tuning the behavior of animals and humans similarly to neurons.
"Importantly, our findings have potential implications for translational medicine, as targeting astrocytic ensembles could lead to more precise and personalized therapeutic approaches for neuropsychiatric disorders," added Navarrete. "The fact that we could alter mouse behavior by selectively manipulating an astrocyte ensemble poses an intriguing question: are astrocytes a substrate for memory? We plan to further investigate the roles of astrocyte ensembles in learning and memory using AstroLight and other cutting-edge tools." More information: Irene Serra et al, Astrocyte ensembles manipulated with AstroLight tune cue-motivated behavior, Nature Neuroscience (2025).
DOI: 10.1038/s41593-025-01870-0 . © 2025 Science X Network.
