FcγR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice
11 affiliations
- 1Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA
- 2Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
- 3Department of Pathology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA
- 4Department of Microbiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA
- 5O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA
- 6Department of Molecular Neuroscience, Graduate School of Medicine, The University of Osaka, Osaka, Japan
- 7Department of Genetics, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA
- 8Department of Biomedical Engineering, University of Alabama at Birmingham School of Engineering, Birmingham, AL, USA
- 9Department of Neurobiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA
- 10Department of Neurobiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA. [email protected]
- 11Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA. [email protected]
Abstract
Chronic neuroinflammation gives rise to diverse microglial states across the brain, yet how region-specific microglial remodeling contributes to cognitive dysfunction remains unclear. Here we report that synapse-engulfing microglia in the thalamus drive cognitive impairment after cortical brain damage in mice, primarily studied in females. Region-specific manipulations of microglia during the chronic phase show that reactive microglial changes in the thalamus, but not in the hippocampus, impair recognition memory. Single-cell RNA sequencing reveals an enrichment of synapse-engulfing CD9 hi microglia in the thalamus. Antibody-based CD9 blockade in the thalamus, as well as microglia-selective CD9 disruption, rescues thalamic synaptic loss, restores neuronal activity, and improves recognition memory. Further analysis shows that the blood-brain barrier disruption and subsequent γ-immunoglobulin (IgG) extravasation facilitate the generation of CD9 hi microglia in an Fcγ receptor III-dependent manner. These findings demonstrate that the induction of synapse-engulfing CD9 hi microglia in the thalamus by IgG/FcγRIII signaling drives recognition memory deficits following cortical damage.
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BibTeX
@article{matoba2026fcγr,
title = {{FcγR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice}},
author = {Ken Matoba and Takahiro Kochi and Oluwaseun Fatoba and Md Sorwer Alam Parvez and Inssaf Berkiks and Yassin Mreyoud and Harrison Strong and Jana H. Badrani and Hency Patel and Yoshiko Nagaoka-Kamata and Masakazu Kamata and Hiroshi Tsujioka and Toshihide Yamashita and David K. Crossman and Minae Niwa and Shin‐ichi Kano},
journal = {Nature Communications},
year = {2026},
month = jul,
doi = {10.1038/s41467-026-74904-1},
url = {https://doi.org/10.1038/s41467-026-74904-1},
note = {CC BY},
}
RIS
TY - JOUR
TI - FcγR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice
AU - Ken Matoba
AU - Takahiro Kochi
AU - Oluwaseun Fatoba
AU - Md Sorwer Alam Parvez
AU - Inssaf Berkiks
AU - Yassin Mreyoud
AU - Harrison Strong
AU - Jana H. Badrani
AU - Hency Patel
AU - Yoshiko Nagaoka-Kamata
AU - Masakazu Kamata
AU - Hiroshi Tsujioka
AU - Toshihide Yamashita
AU - David K. Crossman
AU - Minae Niwa
AU - Shin‐ichi Kano
PY - 2026
DA - 2026/07/09
JO - Nature Communications
DO - 10.1038/s41467-026-74904-1
UR - https://doi.org/10.1038/s41467-026-74904-1
AB - Chronic neuroinflammation gives rise to diverse microglial states across the brain, yet how region-specific microglial remodeling contributes to cognitive dysfunction remains unclear. Here we report that synapse-engulfing microglia in the thalamus drive cognitive impairment after cortical brain damage in mice, primarily studied in females. Region-specific manipulations of microglia during the chronic phase show that reactive microglial changes in the thalamus, but not in the hippocampus, impair recognition memory. Single-cell RNA sequencing reveals an enrichment of synapse-engulfing CD9 hi microglia in the thalamus. Antibody-based CD9 blockade in the thalamus, as well as microglia-selective CD9 disruption, rescues thalamic synaptic loss, restores neuronal activity, and improves recognition memory. Further analysis shows that the blood-brain barrier disruption and subsequent γ-immunoglobulin (IgG) extravasation facilitate the generation of CD9 hi microglia in an Fcγ receptor III-dependent manner. These findings demonstrate that the induction of synapse-engulfing CD9 hi microglia in the thalamus by IgG/FcγRIII signaling drives recognition memory deficits following cortical damage.
SN - 2041-1723
ER -