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Cited by 84Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsGenetics and Neurodevelopmental Disorders

Perisynaptic GluR2-lacking AMPA receptors control the reversibility of synaptic and spines modifications

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Yang, Yunlei, Wang, Xiao-bin, Zhou, Qiang·2010·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0913004107PMC PMC2900706
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Abstract

How persistent synaptic and spine modification is achieved is essential to our understanding of developmental refinement of neural circuitry and formation of memory. Within a short period after their induction, both types of modifications can either be stabilized or reversed, but how this reversibility is controlled is largely unknown. We have shown previously that AMPA receptors (AMPARs) are delivered to perisynaptic regions after the induction of long-term potentiation (LTP) but are absent from perisynaptic regions after the full expression of LTP. Here, we report that perisynaptic AMPARs are GluR2-lacking and they translocate to synapses in a protein kinase C (PKC)-dependent manner. Once entering synapses, these AMPARs quickly switch to GluR2-containing in an activity-dependent manner. Absence of postinduction activity or blocking interactions between GluR2 and NSF, or GluR2 and GRIP/PICK1 results in LTP mediated by GluR2-lacking AMPARs. However, these synaptic GluR2-lacking AMPARs are not sufficient to allow reversibility of LTP. On the other hand, postsynaptic inhibition of PKC activity holds AMPARs at perisynaptic regions. As long as perisynaptic AMPARs are present, both LTP and spine expansion remain labile: they can be reverted to the baseline state together with removal of perisynaptic AMPARs, or they can enter a stabilized state of persistent increase together with synaptic incorporation of perisynaptic AMPARs. Thus, perisynaptic GluR2-lacking AMPARs play a critical role in controlling the reversibility of both synaptic and spine modifications.

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  • The finding that LTP in WT mice was insensitive to IEM1460 is consistent with earlier studies that observed recruitment of GluA2-lacking AMPARs in WT rodents <2 weeks-old and >4 weeks-old but not in the ~3 week-old age range studied.

    “This finding is consistent with several earlier studies using a variety of different protocols to induce LTP that have in general observed recruitment of GluA2-lacking AMPARs in WT rodents <2 weeks-old and >4 weeks-old but not in the ~3 week-old age range that we studied”

    From AKAP150-Anchored Calcineurin Regulates Synaptic Plasticity by Limiting Synaptic Incorporation of Ca<sup>2+</sup>-Permeable AMPA Receptors (2012) · cites this paper as Yang et al., 2010

    The Discussion (page not supplied) reports recruitment of GluR2-lacking AMPARs during some forms of LTP and says induction protocols may account for differing findings. It does not establish the claimed age pattern: recruitment below two weeks and above four weeks, but not around three weeks. The Materials and Methods (page not supplied) specify experiments in P13–P18 rats, not comparisons across those age ranges. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Yang, Y., Wang, X.-B., & Zhou, Q.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Genentech (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2010-06-14
Volume
107
Issue
26
Pages
11999-12004
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0913004107
PMC
PMC2900706
OpenAlex
W2074423856
Cited by
84
References
7
Citations by year
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FWCI
2.98
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Genentech
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
long-term potentiation, dendritic spine morphogenesis, protein kinase C, NSF, memory formation
MeSH terms
Animals, Carrier Proteins, Cytoskeletal Proteins, Memory, Nerve Tissue Proteins, Nuclear Proteins, Protein Kinase C, Synapses, Rats, Sprague-Dawley, Long-Term Potentiation, Receptors, AMPA, Intracellular Signaling Peptides and Proteins, Dendritic Spines, Rats, N-Ethylmaleimide-Sensitive Proteins, In Vitro Techniques

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