FcγR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice
- Ken Matoba
- Takahiro Kochi
- Oluwaseun Fatoba
- Md. Sorwer Alam Parvez
- Inssaf Berkiks
- Yassin R. Mreyoud
- Harrison Strong
- Jana H. Badrani
- Hency Patel
- Yoshiko Nagaoka-Kamata
- Masakazu Kamata
- Hiroshi Tsujioka
- Toshihide Yamashita
- David K. Crossman
- Minae Niwa
- Shin-ichi Kano
2026-07-09
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.