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Cited by 210Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersMemory and Neural Mechanisms

NMDA Receptor-Dependent LTD Requires Transient Synaptic Incorporation of Ca 2+ -Permeable AMPARs Mediated by AKAP150-Anchored PKA and Calcineurin

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Sanderson, Jennifer L., Gorski, Jessica A., Dell’Acqua, Mark L.·2016·Neuron
DOI 10.1016/j.neuron.2016.01.043PMC PMC4914360
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Abstract

Information processing in the brain requires multiple forms of synaptic plasticity that converge on regulation of NMDA and AMPA-type glutamate receptors (NMDAR, AMPAR), including long-term potentiation (LTP) and long-term depression (LTD) and homeostatic scaling. In some cases, LTP and homeostatic plasticity regulate synaptic AMPAR subunit composition to increase the contribution of Ca(2+)-permeable receptors (CP-AMPARs) containing GluA1 but lacking GluA2 subunits. Here, we show that PKA anchored to the scaffold protein AKAP150 regulates GluA1 phosphorylation and plays a novel role controlling CP-AMPAR synaptic incorporation during NMDAR-dependent LTD. Using knockin mice that are deficient in AKAP-anchoring of either PKA or the opposing phosphatase calcineurin, we found that CP-AMPARs are recruited to hippocampal synapses by anchored PKA during LTD induction but are then rapidly removed by anchored calcineurin. Importantly, blocking CP-AMPAR recruitment, removal, or activity interferes with LTD. Thus, CP-AMPAR synaptic recruitment is required to transiently augment NMDAR Ca(2+) signaling during LTD induction.

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  • CP-AMPARs have faster decay kinetics but large conductance, enhancing synaptic transmission, and may activate unique Ca2+-sensitive signaling pathways which lead to opening of a metaplastic state, in which synapses become primed for LTD or LTP.

    “These receptors have faster decay kinetics but large conductance, enhancing synaptic transmission, and may activate unique Ca2+-sensitive signaling pathways which lead to an opening of a metaplastic state, in which synapses become primed for LTD or LTP (Clem and Huganir, 2010, Sanderson et al., 2016).”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Sanderson et al., 2016

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • The presence of perisynaptic CP-AMPARs as well as their recruitment to synapses requires signaling from PKA and the S845 phosphorylation site.

    “The presence of perisynaptic CP-AMPARs as well as their recruitment to synapses requires signaling from PKA and the S845 phosphorylation site (He et al., 2009, Clem and Huganir, 2010, Sanderson et al., 2016).”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Sanderson et al., 2016

    The Introduction reports PKA-dependent recruitment of CP-AMPARs to synapses during LTD induction, and the Discussion says a perisynaptic CP-AMPAR pool was absent in S845A mice (page numbers unavailable). The paper does not establish that PKA signaling is required for the presence of that perisynaptic pool; it also acknowledges uncertainty about whether recruitment is physical or functional. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Peri-synaptic CP-AMPARs (GluA1 homomers) are transiently recruited to the synapse during the induction of LTD in a PKA-dependent manner.

    “It has been recently shown that this population of peri-synaptic CP-AMPARs (GluA1 homomers) are transiently recruited to the synapse during the induction of LTD in a PKA-dependent manner (Sanderson et al., 2016).”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Sanderson et al., 2016

    The Introduction and Results state that GluA1 CP-AMPARs are transiently recruited during LTD induction through AKAP150-anchored PKA signaling. However, the Discussion says the experiments cannot distinguish physical recruitment into the synapse from functional engagement of receptors already at peri-synaptic locations. The claim presents physical recruitment of a peri-synaptic population as settled; page numbers were not supplied in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The involvement of CP-AMPARs in hippocampal LTP may follow a very narrow developmental window of only a few days.

    “These findings show that the involvement of CP-AMPARs in hippocampal LTP may follow a very narrow developmental window of only a few days.”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Sanderson et al., 2016

  • Hippocampal LTP in very young neurons may preferentially recruit CP-AMPARs.

    “Hippocampal LTP in very young neurons may preferentially recruit CP-AMPARs (Plant et al., 2006, Sanderson et al., 2016).”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Sanderson et al., 2016

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Sorted by citations

Authors
Sanderson, J. L., Gorski, J. A., & Dell’Acqua, M. L.
Affiliations
University of Colorado Anschutz (US)
Corresponding author
Dell’Acqua, Mark L.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2016-03
Volume
89
Issue
5
Pages
1000-1015
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2016.01.043
PMC
PMC4914360
OpenAlex
W2289953129
Cited by
210
References
14
Citations by year
2026: 8 · 2025: 19 · 2024: 25 · 2023: 19 · 2022: 28 · 2021: 30 · 2020: 16 · 2019: 19 · 2018: 24 · 2017: 13 · 2016: 8 · 2015: 1
FWCI
12.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS040701)
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
calcium-permeable AMPA receptors, GluA1 phosphorylation, AKAP150, protein kinase A, calcineurin, AMPA receptor subunit composition, GluA2, hippocampus, synaptic plasticity
MeSH terms
Animals, Calcium, Electric Stimulation, Enzyme Inhibitors, Hippocampus, Mice, Inbred C57BL, Mice, Transgenic, Models, Molecular, Mutation, Synapses, Receptors, N-Methyl-D-Aspartate, Silver Staining, Cyclic AMP-Dependent Protein Kinases, Receptors, AMPA, Excitatory Amino Acid Agents, Calcineurin, Long-Term Synaptic Depression, Mice, A Kinase Anchor Proteins, Synaptic Potentials

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