Anxiety control by astrocytes in the lateral habenula
Open accessAbstract
The potential role of astrocytes in lateral habenula (LHb) in modulating anxiety was explored in this study. The habenula are a pair of small nuclei located above the thalamus, known for their involvement in punishment avoidance and anxiety. Herein, we observed an increase in theta-band oscillations of local field potentials (LFPs) in the LHb when mice were exposed to anxiety-inducing environments. Electrical stimulation of LHb at theta-band frequency promoted anxiety-like behavior. Calcium (Ca2+) levels and pH in the cytosol of astrocytes and local brain blood volume changes were studied in mice expressing either a Ca2+ or a pH sensor protein specifically in astrocytes and mScarlet fluorescent protein in the blood plasma using fiber photometry. An acidification response to anxiety was observed. Photoactivation of archaerhopsin-T (ArchT), an optogenetic tool that acts as an outward proton pump, results in intracellular alkalinization. Photostimulation of LHb in astrocyte-specific ArchT-expressing mice resulted in dissipation of theta-band LFP oscillation in an anxiogenic environment and suppression of anxiety-like behavior. These findings provide evidence that LHb astrocytes modulate anxiety and may offer a new target for treatment of anxiety disorders.
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Astrocytes and the vasculature may not only respond passively to neuronal activity but may also exhibit dynamics that precede changes in neuronal network states.
“Together, these findings suggest that astrocytes and the vasculature may not only respond passively to neuronal activity but may also exhibit dynamics that precede changes in neuronal network states39,53–55.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [39]
The Discussion (p. 14) proposes that astrocytic activity can lead to theta-band oscillations in the lateral habenula, supporting the possibility that astrocytes help shape neuronal states rather than merely respond to them. The passage on brain blood volume during REM sleep (p. 10) describes an associated vascular change, but does not say that vascular dynamics precede changes in neuronal network states. (LLM, conf=0.82)
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Dynamics of Neuronal and Astrocytic Energy Molecules in Epilepsy
Furukawa, K., Ikoma, Y., Niino, Y., Hiraoka, Y., Tanaka, K., Miyawaki, A., Hirrlinger, J., & Matsui, K. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70044 · Cited by 11 · see citing works
Self-citationEnergy paradox in REM sleep: balancing supply and consumption in brain metabolism
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“Together, these fi ndings suggest that astrocytes and the vasculature may not only respond passively to neuronal activity but may alsoexhibitdynamicsthatprecedechangesinneuronalnetworkstates 39,53 – 55 .”
Self-citation
- Authors
- Tan, W., Ikoma, Y., Takahashi, Y., Konno, A., Hirai, H., Hirase, H., & Matsui, K.
- Affiliations
- Tohoku University (JP)
- Gunma University (JP)
- University of Copenhagen (DK)
- Corresponding author
- Matsui, Ko
- Venue
- Neuroscience Research
- Publisher
- Elsevier BV
- Published
- 2024-08
- Volume
- 205
- Pages
- 1-15
- ISSN
- 0168-0102 (ISSN-L)
- OpenAlex
- W4391486105
- Cited by
- 20
- References
- 75
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 4
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neuroscience Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Takeda Science Foundation
- Uehara Memorial Foundation
- AMED
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- astrocytes, lateral habenula, anxiety, theta oscillations, local field potentials, blood volume, optogenetics, anxiety-like behavior, anxiety disorders
- MeSH terms
- Animals, Anxiety, Astrocytes, Calcium, Male, Mice, Inbred C57BL, Mice, Transgenic, Theta Rhythm, Habenula, Mice
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