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Impermanence of dendritic spines in live adult CA1 hippocampus
Open accessAbstract
The mammalian hippocampus is crucial for episodic memory formation and transiently retains information for about 3-4 weeks in adult mice and longer in humans. Although neuroscientists widely believe that neural synapses are elemental sites of information storage, there has been no direct evidence that hippocampal synapses persist for time intervals commensurate with the duration of hippocampal-dependent memory. Here we tested the prediction that the lifetimes of hippocampal synapses match the longevity of hippocampal memory. By using time-lapse two-photon microendoscopy in the CA1 hippocampal area of live mice, we monitored the turnover dynamics of the pyramidal neurons' basal dendritic spines, postsynaptic structures whose turnover dynamics are thought to reflect those of excitatory synaptic connections. Strikingly, CA1 spine turnover dynamics differed sharply from those seen previously in the neocortex. Mathematical modelling revealed that the data best matched kinetic models with a single population of spines with a mean lifetime of approximately 1-2 weeks. This implies ∼100% turnover in ∼2-3 times this interval, a near full erasure of the synaptic connectivity pattern. Although N-methyl-d-aspartate (NMDA) receptor blockade stabilizes spines in the neocortex, in CA1 it transiently increased the rate of spine loss and thus lowered spine density. These results reveal that adult neocortical and hippocampal pyramidal neurons have divergent patterns of spine regulation and quantitatively support the idea that the transience of hippocampal-dependent memory directly reflects the turnover dynamics of hippocampal synapses.
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“Perhaps even more problematic is the report that a substantial portion of dendritic spines on CA1 pyramidal cells turn over within a few weeks (416, 417).”
From Synaptic memory and CaMKII (2023) · cites this paper as [416]
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Metadata
- Authors
- Attardo, A., Fitzgerald, J. E., & Schnitzer, M. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Stanford University (US)
- Corresponding author
- Schnitzer, Mark J.
- Venue
- Nature
- Published
- 2015-06-22
- Volume
- 523
- Issue
- 7562
- Pages
- 592-596
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4648621
- OpenAlex
- W1655792606
- Cited by
- 399
- References
- 34
- Citations by year
- 2026: 23 · 2025: 43 · 2024: 29 · 2023: 43 · 2022: 39 · 2021: 45 · 2020: 38 · 2019: 34 · 2018: 31 · 2017: 32 · 2016: 35 · 2015: 7
- FWCI
- 16.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute on Aging (R21AG038771)
- National Institute of Mental Health (R21MH092809)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- hippocampal CA1, synaptic plasticity, episodic memory, NMDA receptor, pyramidal neurons, synaptic connectivity, microendoscopy, spine density, adult mice, NMDA receptor blockade
- MeSH terms
- Animals, Endoscopy, Kinetics, Male, Neuronal Plasticity, Synapses, Time Factors, Receptors, N-Methyl-D-Aspartate, Photons, Pyramidal Cells, Neocortex, Dendritic Spines, Mice, CA1 Region, Hippocampal, Memory, Episodic
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