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Cited by 139Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsTreatment of Major Depression

Long-term depression triggers the selective elimination of weakly integrated synapses

Open access
Wiegert, J. Simon, Oertner, Thomas G.·2013·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1315926110PMC PMC3839749
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Abstract

Long-term depression (LTD) weakens synaptic transmission in an activity-dependent manner. It is not clear, however, whether individual synapses are able to maintain a depressed state indefinitely, as intracellular recordings rarely exceed 1 h. Here, we combine optogenetic stimulation of identified Schaffer collateral axons with two-photon imaging of postsynaptic calcium signals and follow the fate of individual synapses for 7 d after LTD induction. Optogenetic stimulation of CA3 pyramidal cells at 1 Hz led to strong and reliable depression of postsynaptic calcium transients in CA1. NMDA receptor activation was necessary for successful induction of LTD. We found that, in the days following LTD, many depressed synapses and their "neighbors" were eliminated from the hippocampal circuit. The average lifetime of synapses on nonstimulated dendritic branches of the same neurons remained unaffected. Persistence of individual depressed synapses was highly correlated with reliability of synaptic transmission, but not with spine size or the amplitude of spine calcium transients. Our data suggest that LTD initially leads to homogeneous depression of synaptic function, followed by selective removal of unreliable synapses and recovery of function in the persistent fraction.

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  • Spine shrinkage tends to spread, as in LTD.

    “It has been reported that spine shrinkage tends to spread919 as in the case with LTD202122.”

    From State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines (2016) · cites this paper as [19]

    The Discussion reports that LTD induction destabilized stimulated spines and their neighbors, but says that depression of synaptic efficacy *might* have spread to neighboring synapses; it does not establish that LTD itself tends to spread. It also reports no immediate spine shrinkage under this study’s stimulation protocol. Page numbers are unavailable in our copy. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Wiegert, J. S., & Oertner, T. G.
Affiliations
Institute for Synaptic Physiology, Center for Molecular Neurobiology Hamburg, D-20251 Hamburg, Germany
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2013-11-04
Volume
110
Issue
47
Pages
E4510-9
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1315926110
PMC
PMC3839749
OpenAlex
W2128795925
Cited by
139
References
12
Citations by year
2026: 4 · 2025: 11 · 2024: 11 · 2023: 3 · 2022: 10 · 2021: 10 · 2020: 10 · 2019: 10 · 2018: 12 · 2017: 20 · 2016: 18 · 2015: 10 · 2014: 10
FWCI
6.22
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
long-term depression, synaptic pruning, synaptic plasticity, Schaffer collaterals, NMDA receptor, dendritic spine morphology, hippocampus, optogenetic stimulation, two-photon calcium imaging
MeSH terms
Channelrhodopsins, Animals, Fluorescence, Hippocampus, Synaptic Transmission, Neuronal Plasticity, Synapses, Rats, Wistar, Pyramidal Cells, Electroporation, Patch-Clamp Techniques, Calcium Signaling, Long-Term Synaptic Depression, Rats, Optogenetics

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