| First Author | Nguyen PT | Year | 2020 |
| Journal | Cell | Volume | 182 |
| Issue | 2 | Pages | 388-403.e15 |
| PubMed ID | 32615087 | Mgi Jnum | J:295370 |
| Mgi Id | MGI:6448295 | Doi | 10.1016/j.cell.2020.05.050 |
| Citation | Nguyen PT, et al. (2020) Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity. Cell 182(2):388-403.e15 |
| abstractText | Synapse remodeling is essential to encode experiences into neuronal circuits. Here, we define a molecular interaction between neurons and microglia that drives experience-dependent synapse remodeling in the hippocampus. We find that the cytokine interleukin-33 (IL-33) is expressed by adult hippocampal neurons in an experience-dependent manner and defines a neuronal subset primed for synaptic plasticity. Loss of neuronal IL-33 or the microglial IL-33 receptor leads to impaired spine plasticity, reduced newborn neuron integration, and diminished precision of remote fear memories. Memory precision and neuronal IL-33 are decreased in aged mice, and IL-33 gain of function mitigates age-related decreases in spine plasticity. We find that neuronal IL-33 instructs microglial engulfment of the extracellular matrix (ECM) and that its loss leads to impaired ECM engulfment and a concomitant accumulation of ECM proteins in contact with synapses. These data define a cellular mechanism through which microglia regulate experience-dependent synapse remodeling and promote memory consolidation. |
