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Perineuronal nets stabilize the grid cell network
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Abstract
Grid cells are part of a widespread network which supports navigation and spatial memory. Stable grid patterns appear late in development, in concert with extracellular matrix aggregates termed perineuronal nets (PNNs) that condense around inhibitory neurons. It has been suggested that PNNs stabilize synaptic connections and long-term memories, but their role in the grid cell network remains elusive. We show that removal of PNNs leads to lower inhibitory spiking activity, and reduces grid cells' ability to create stable representations of a novel environment. Furthermore, in animals with disrupted PNNs, exposure to a novel arena corrupted the spatiotemporal relationships within grid cell modules, and the stored representations of a familiar arena. Finally, we show that PNN removal in entorhinal cortex distorted spatial representations in downstream hippocampal neurons. Together this work suggests that PNNs provide a key stabilizing element for the grid cell network.
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“and in V1 visual cortex, ChABC decreases both excitatory and inhibitory inputs to PV interneurons [46, 47].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [46]
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“Both hippocampus and perirhinal cortex are rich in PV interneurons enwrapped with PNNs, and PNNs are also present on some hippocampal pyramidal neurons [46, 101, 102].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [46]
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“All the social memory associated regions are highly populated with PNN-surrounded PV neurons [46, 66, 130, 131].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [46]
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“while in the entorhinal cortex, ChABC reduces inhibitory inputs”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [46]
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“Following PNN removal in entorhinal cortex there are distorted spatial representations in downstream hippocampal neurons (Fig. 2C) [46].”
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“This suggests that PNNs contribute to ensure a rigid grid cell network, which is essential for new representations to form, and that the heightened network plasticity caused by PNN removal interferes with stored spatial representations and perhaps memories.”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [46]
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“However, degradation of PNNs in medial entorhinal cortex, where PV positive neurons are enwrapped in particularly dense PNNs, destabilizes the grid cell networks leading to impaired representations of new environments [46].”
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“This suggests that PNNs contribute to ensure a rigid grid cell network, which is essential for new representations to form, and that the heightened network plasticity caused by PNN removal interferes with stored spatial representations and perhaps memories.”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [46]
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“The higher performance in prokaryotes is consistent with previous observations regarding the availability of evolutionary information in prokaryotes compared to Eukarya27 (Supplementary Fig. 1).”
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“Another recently published method obtains AUC 0.76 on this set27.”
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“We used 1661 protein complexes with known interfaces from a recent study27 to test the developed pipeline.”
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“The study of AF2s ability to separate interacting and non-interacting proteins here contains more extensive data than recent studies27.”
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“Pairing the correct sequences should result in MSAs containing inter-chain co-evolutionary information27.”
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“PLCG2 polymorphisms are associated with both reduced and increased risk of Alzheimer’s disease (AD) and with longevity.”
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Metadata
- Authors
- Christensen, A. C., Lensjø, K. K., Lepperød, M. E., Dragly, S.-A., Sutterud, H., Blackstad, J. S., Fyhn, M., & Hafting, T.
- Affiliations
- University of Oslo (NO)
- Corresponding author
- Hafting, Torkel
- ORCID
- Venue
- Nature Communications
- Published
- 2021-01-11
- Volume
- 12
- Issue
- 1
- Pages
- 253-253
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7801665
- OpenAlex
- W3120392574
- Cited by
- 1,865
- References
- 76
- Citations by year
- 2026: 132 · 2025: 277 · 2024: 340 · 2023: 431 · 2022: 499 · 2021: 170
- FWCI
- 189.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- Norges Forskningsråd (217920, 231248)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Spatial Cognition and Navigation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- perineuronal nets, grid cells, extracellular matrix, inhibitory interneurons, spatial memory, navigation, entorhinal cortex, hippocampus, synaptic stability
- MeSH terms
- Grid Cells, Action Potentials, Animals, Computer Simulation, Hippocampus, Male, Models, Neurological, Neurons, Theta Rhythm, Time Factors, Entorhinal Cortex, Rats, Long-Evans, Rats
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