ArticleProceedings of the National Academy of Sciences of the United States of America2013
Very long-term memories may be stored in the pattern of holes in the perineuronal net.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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Who cites it
137 citing papers in PubMed.
- Blocking human fear memory with the matrix metalloproteinase inhibitor doxycycline.Molecular psychiatry · 2018Trial
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- Reductionism in Engram Neuroscience.The European journal of neuroscience · 2026Review
- PKM ζ-PKC ι / λ double-knockout demonstrates atypical PKC is crucial for the persistence of hippocampal LTP and spatial memory.bioRxiv : the preprint server for biology · 2026Article
- Ventral pallidal perineuronal nets regulate opioid relapse.bioRxiv : the preprint server for biology · 2026Article
- Clozapine induces perineuronal net remodeling in a developmental mouse model exhibiting schizophrenia-relevant phenotypes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Midbrain extracellular matrix and microglia are associated with cognition in aging mice.Nature communications · 2025Article
- Sex and experience dependent regulation of synaptic protein turnover.bioRxiv : the preprint server for biology · 2025Article
- Paxillin's nuclear switch: orchestrating gene splicing for brain plasticity.The EMBO journal · 2025Article
- Degradation of perineuronal nets in hippocampal CA2 explains the loss of social cognition memory in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- PV - Oligodendrocyte Interactions in the Infralimbic Cortex Promote Extracellular Plasticity after Safety Learning.bioRxiv : the preprint server for biology · 2025Article
- Long-term potentiation-induced changes in actin dynamics and spine geometry persist on the timescale of the synaptic tag.Communications biology · 2025Article
- Distribution of perineuronal nets in the adult rat neocortex.Somatosensory & motor research · 2025Article
- Disruption of Extracellular Matrix and Perineuronal Nets Modulates Extracellular Space Volume and Geometry.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Displacement of extracellular chloride by immobile anionic constituents of the brain's extracellular matrix.The Journal of physiology · 2025Article
- What are memories made of? A survey of neuroscientists on the structural basis of long-term memory.PloS one · 2025Article
- Intergenerational Effects of Stress - A Focus on Learning and Memory.Current topics in behavioral neurosciences · 2025Review
77 more citing papers are in PubMed but not listed here.
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Abstract
A hypothesis and the experiments to test it propose that very long-term memories, such as fear conditioning, are stored as the pattern of holes in the perineuronal net (PNN), a specialized ECM that envelops mature neurons and restricts synapse formation. The 3D intertwining of PNN and synapses would be imaged by serial-section EM. Lifetimes of PNN vs. intrasynaptic components would be compared with pulse-chase (15)N labeling in mice and (14)C content in human cadaver brains. Genetically encoded indicators and antineoepitope antibodies should improve spatial and temporal resolution of the in vivo activity of proteases that locally erode PNN. Further techniques suggested include genetic KOs, better pharmacological inhibitors, and a genetically encoded snapshot reporter, which will capture the pattern of activity throughout a large ensemble of neurons at a time precisely defined by the triggering illumination, drive expression of effector genes to mark those cells, and allow selective excitation, inhibition, or ablation to test their functional importance. The snapshot reporter should enable more precise inhibition or potentiation of PNN erosion to compare with behavioral consequences. Finally, biosynthesis of PNN components and proteases would be imaged.
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