ArticleNature2014
Synapse elimination and learning rules co-regulated by MHC class I H2-Db.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
142 citing papers in PubMed, 2 syntheses or guidelines pooled it, 229 citations in OpenAlex.
- Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review.Molecular neurobiology · 2022Pooled it
- A genome-wide association study reveals a substantial genetic basis underlying the Ebbinghaus illusion.Journal of human genetics · 2021Pooled it
- Immune dysregulation in mania: A proof-of-concept platelet proteomics study.Psychiatry and clinical neurosciences · 2026Article
- Synaptic pruning, myelination and the emergence of psychiatric disorders in late adolescence.bioRxiv : the preprint server for biology · 2026Article
- Article
- Enhanced Anti-Nociception by Novel Dual Antagonists for 5-HT2AR and mGluR5 in Preclinical Models of Pain.Biomolecules · 2025Article
- Eye-specific differences in active zone addition during synaptic competition in the developing visual system.bioRxiv : the preprint server for biology · 2025Article
- Review
- C4d, a high-affinity LilrB2 ligand, is elevated in Alzheimer's disease and mediates synapse pruning.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The neuroimmune connectome in health and disease.Nature · 2025Review
- Review
- Activity-Dependent Synapse Refinement: From Mechanisms to Molecules.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Stearoyl-CoA desaturase-1: a potential therapeutic target for neurological disorders.Molecular neurodegeneration · 2024Review
- An innate immune response to adeno-associated virus genomes decreases cortical dendritic complexity and disrupts synaptic transmission.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Immune receptors and aging brain.Bioscience reports · 2024Review
- Contactomics of Microglia and Intercellular Communication.Advances in neurobiology · 2024Review
- Ocular Necessities: A Neuroethological Perspective on Vertebrate Visual Development.Brain, behavior and evolution · 2024Review
- Evidence that Alzheimer's Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry.Journal of Alzheimer's disease : JAD · 2024Review
- Interrogating the Etiology of Sporadic Alzheimer's Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Outside-in signaling through the major histocompatibility complex class-I cytoplasmic tail modulates glutamate receptor expression in neurons.Scientific reports · 2023Article
82 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The formation of precise connections between retina and lateral geniculate nucleus (LGN) involves the activity-dependent elimination of some synapses, with strengthening and retention of others. Here we show that the major histocompatibility complex (MHC) class I molecule H2-D(b) is necessary and sufficient for synapse elimination in the retinogeniculate system. In mice lacking both H2-K(b) and H2-D(b) (K(b)D(b)(-/-)), despite intact retinal activity and basal synaptic transmission, the developmentally regulated decrease in functional convergence of retinal ganglion cell synaptic inputs to LGN neurons fails and eye-specific layers do not form. Neuronal expression of just H2-D(b) in K(b)D(b)(-/-) mice rescues both synapse elimination and eye-specific segregation despite a compromised immune system. When patterns of stimulation mimicking endogenous retinal waves are used to probe synaptic learning rules at retinogeniculate synapses, long-term potentiation (LTP) is intact but long-term depression (LTD) is impaired in K(b)D(b)(-/-) mice. This change is due to an increase in Ca(2+)-permeable AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Restoring H2-D(b) to K(b)D(b)(-/-) neurons renders AMPA receptors Ca(2+) impermeable and rescues LTD. These observations reveal an MHC-class-I-mediated link between developmental synapse pruning and balanced synaptic learning rules enabling both LTD and LTP, and demonstrate a direct requirement for H2-D(b) in functional and structural synapse pruning in CNS neurons.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.