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Cited by 470Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersMemory and Neural Mechanisms

PSD-95 is required for activity-driven synapse stabilization.

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Ehrlich, Ingrid, Klein, Matthew, Rumpel, Simon, Malinow, Roberto·2007·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0609307104PMC PMC1820728
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Abstract

The activity-dependent regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors and the stabilization of synapses are critical to synaptic development and plasticity. One candidate molecule implicated in maturation, synaptic strengthening, and plasticity is PSD-95. Here we find that acute knockdown of PSD-95 in brain slice cultures by RNAi arrests the normal development of synaptic structure and function that is driven by spontaneous activity. Surprisingly, PSD-95 is not necessary for the induction and early expression of long-term potentiation (LTP). However, knockdown of PSD-95 leads to smaller increases in spine size after chemically induced LTP. Furthermore, although at this age spine turnover is normally low and LTP produces a transient increase, in cells with reduced PSD-95 spine turnover is high and remains increased after LTP. Taken together, our data support a model in which appropriate levels of PSD-95 are required for activity-dependent synapse stabilization after initial phases of synaptic potentiation.

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Cited by

Sorted by citations

Authors
Ehrlich, I., Klein, M., Rumpel, S., & Malinow, R.
Affiliations
  • Cold Spring Harbor Laboratory (US)
  • Johns Hopkins University (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2007-03-06
Volume
104
Issue
10
Pages
4176-4181
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0609307104
PMC
PMC1820728
OpenAlex
W2029015906
Cited by
470
References
8
Citations by year
2026: 22 · 2025: 20 · 2024: 15 · 2023: 18 · 2022: 23 · 2021: 24 · 2020: 28 · 2019: 25 · 2018: 26 · 2017: 28 · 2016: 31 · 2015: 27 · 2014: 27 · 2013: 32 · 2012: 20
FWCI
10.02
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (R01MH049159)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
PSD-95, synapse stabilization, activity-dependent synaptic plasticity, AMPA receptors, long-term potentiation, dendritic spines, spontaneous activity, synaptic development, brain slice culture, RNAi knockdown
MeSH terms
Disks Large Homolog 4 Protein, Animals, Brain, Dendrites, Electrophysiology, Glutamine, Hippocampus, Image Processing, Computer-Assisted, Membrane Proteins, Synaptic Transmission, Neuronal Plasticity, Synapses, Long-Term Potentiation, Receptors, AMPA, RNA Interference, Intracellular Signaling Peptides and Proteins, Rats

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