| First Author | Matoba K | Year | 2026 |
| Journal | Nat Commun | Volume | 17 |
| Issue | 1 | PubMed ID | 42425959 |
| Mgi Jnum | J:392170 | Mgi Id | MGI:8403254 |
| Doi | 10.1038/s41467-026-74904-1 | Citation | Matoba K, et al. (2026) FcgammaR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice. Nat Commun 17(1) |
| abstractText | 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 gamma-immunoglobulin (IgG) extravasation facilitate the generation of CD9(hi) microglia in an Fcgamma receptor III-dependent manner. These findings demonstrate that the induction of synapse-engulfing CD9(hi) microglia in the thalamus by IgG/FcgammaRIII signaling drives recognition memory deficits following cortical damage. |
