Prefrontal cortex astrocytes modulate distinct neuronal populations to control anxiety-like behavior

Eunyoung Kim, Hairuo Du, Yanqi Tan, Brandon L. Brown, Yaowen Chang, Blanca Díaz-Castro, Jonathan V. Sweedler and Xinzhu Yu ()
Additional contact information
Eunyoung Kim: University of Illinois at Urbana-Champaign
Hairuo Du: University of Illinois at Urbana-Champaign
Yanqi Tan: University of Illinois at Urbana-Champaign
Brandon L. Brown: University of Illinois at Urbana-Champaign
Yaowen Chang: University of Illinois at Urbana-Champaign
Blanca Díaz-Castro: University of Edinburgh
Jonathan V. Sweedler: University of Illinois at Urbana-Champaign
Xinzhu Yu: University of Illinois at Urbana-Champaign

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Accumulating evidence has supported diverse regulatory functions of astrocytes in different neural circuits as well as various aspects of complex behaviors. However, little is known about how astrocytes regulate different neuronal subpopulations that are linked to specific behavioral aspects within a single brain region. Here, we show that astrocytes in the medial prefrontal cortex (mPFC) encode anxiogenic environmental cues in freely behaving mice. Silencing mPFC astrocyte Ca2+ signaling heightens anxiety-like behavior and triggers opposing functional responses in excitatory and inhibitory neurons. Moreover, neuronal subpopulations tuned to anxiety-like behavior are differentially modulated by mPFC astrocytes at single cell and network levels. Using cell type-specific proximity biotinylation approaches, we identified significant intracellular and intercellular proteomic alterations in mPFC astrocytes and at the astrocyte-neuron interface associated with anxiety. Collectively, our findings uncover mechanisms underpinning the heterogenous astrocyte-neuron interaction that is behaviorally relevant and offer critical insights into the pathophysiology of emotional disorders.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63131-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63131-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63131-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().