ArticleProceedings of the National Academy of Sciences of the United States of America2022
The nonclassical MHC class I Qa-1 expressed in layer 6 neurons regulates activity-dependent plasticity via microglial CD94/NKG2 in the cortex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 19 citations in OpenAlex.
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- Human neuronal maturation comes of age: cellular mechanisms and species differences.Nature reviews. Neuroscience · 2024Review
- Natural variation in oxytocin receptor signaling causes widespread changes in brain transcription: a link to the natural killer gene complex.bioRxiv : the preprint server for biology · 2023Article
- Outside-in signaling through the major histocompatibility complex class-I cytoplasmic tail modulates glutamate receptor expression in neurons.Scientific reports · 2023Article
- Characterization of large-scale genomic differences in the first complete human genome.Genome biology · 2023Article
- Rabies virus-based labeling of layer 6 corticothalamic neurons for two-photon imagingiScience · 2023Article
- The molecular signals that regulate activity-dependent synapse refinement in the brain.Current opinion in neurobiology · 2023Review
- Visual Cortical Plasticity: Molecular Mechanisms as Revealed by Induction Paradigms in Rodents.International journal of molecular sciences · 2023Review
- Glia as antigen-presenting cells in the central nervous system.Current opinion in neurobiology · 2022Review
- Synapse-specific plasticity relies on neuroimmune interactions.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Abstract
During developmental critical periods, circuits are sculpted by a process of activity-dependent competition. The molecular machinery involved in regulating the complex process of responding to different levels of activity is now beginning to be identified. Here, we show that the nonclassical major histocompatibility class I (MHCI) molecule Qa-1 is expressed in the healthy brain in layer 6 corticothalamic neurons. In the visual cortex, Qa-1 expression begins during the critical period for ocular dominance (OD) plasticity and is regulated by neuronal activity, suggesting a role in regulating activity-dependent competition. Indeed, in mice lacking Qa-1, OD plasticity is perturbed. Moreover, signaling through CD94/NKG2, a known cognate Qa-1 heterodimeric receptor in the immune system, is implicated: selectively targeting this interaction phenocopies the plasticity perturbation observed in Qa-1 knockouts. In the cortex, CD94/NKG2 is expressed by microglial cells, which undergo activity-dependent changes in their morphology in a Qa-1–dependent manner. Our study thus reveals a neuron–microglial interaction dependent upon a nonclassical MHCI molecule expressed in L6 neurons, which regulates plasticity in the visual cortex. These results also point to an unexpected function for the Qa-1/HLA-E (ligand) and CD94/NKG2 (receptor) interaction in the nervous system, in addition to that described in the immune system.
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