ArticleResearch square2023
Cationic peptides erase memories by removing synaptic AMPA receptors through endophilin-mediated endocytosis.
Eric Stokes, Yinyin Zhuang, Michael Toledano, Jose Vasquez, Ghalia Azouz, May Hui, Isabella Tyler, Xiaoyu Shi, Jason Aoto, Kevin T Beier
Open access · greenAbstract readPreprint
In one paragraphArticle in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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0citing papers in PubMed
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What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registryThe trial behind it
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3 · Its place in the literatureWho cites it
0 citing papers in PubMed, 0 citations in OpenAlex.
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
10 authors at 2 institutions in 1 country.
Eric StokesPharmacology Graduate Program, University of Colorado Anschutz, Aurora, CO 80045, USA.
Yinyin ZhuangDepartment of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.
Michael ToledanoDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA 92697-4560.
Ghalia AzouzDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA 92697-4560.
May HuiDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA 92697-4560.
Jason AotoPharmacology Graduate Program, University of Colorado Anschutz, Aurora, CO 80045, USA.
University of California, Irvine · USUniversity of Colorado Anschutz Medical Campus · US
Funding
Circuitry dynamics underlying opioid-dependence: Integrating structural, functional, and transcriptomic mechanismsR01DA056599 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI KEVIN T BEIER, Julie A Blendy · 2022 to 2026
$3.8MSculpting the brain: High-resolution spatiotemporally-controlled modulation of memoriesDP2AG067666 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BEIER, KEVIN T, CORDER, GREGORY · 2019 to 2022
$3.1MGel-based Optical-isolation Single-Cell 3D Spatial MultiomicsDP2GM150017 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI SHI, XIAOYU · 2022 to 2025
$2.6MMapping opioid-dependence state transitions across structural, functional, and transcriptomic topologiesR01DA054374 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI BLENDY, JULIE A, CORDER, GREGORY · 2021 to 2025
$2.4MFunctional and mechanistic interrogation of alpha neurexin extracellular domainsR01MH116901 · NIMH · UNIVERSITY OF COLORADO DENVER · PI AOTO, JASON · 2018 to 2022
$1.9MInvestigation of neural ensembles driving pain chronificationR01NS130044 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI KEVIN T BEIER, Gregory Corder · 2023 to 2026
$1.4MINVESTIGATING FUNCTION OF NOVEL DRUG-INDUCED SYNAPTIC CHANGES IN THE VTAR00DA041445 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BEIER, KEVIN T · 2018 to 2020
$747kElucidating How Primary Cilia Regulate Hedgehog Signaling by Super-Resolution MicroscopyR00GM126136 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI SHI, XIAOYU · 2020 to 2022
$746kControl of subsynaptic domain organization and nanocolumn alignment by neurexin-3R21MH129620 · NIMH · UNIVERSITY OF COLORADO DENVER · PI AOTO, JASON · 2022 to 2023
$408kInvestigation of neural ensembles underlying chronic painF30DA056215 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI May Hui · 2022 to 2026
$189kNIA NIH HHS DP2 AG067666NIDA NIH HHS F30 DA056215NIDA NIH HHS R00 DA041445NIDA NIH HHS R01 DA054374NIDA NIH HHS R01 DA056599NIGMS NIH HHS DP2 GM150017NIGMS NIH HHS R00 GM126136NIMH NIH HHS R01 MH116901NIMH NIH HHS R21 MH129620NINDS NIH HHS R01 NS130044
6 · The paper itselfAbstract
Administration of the Zeta Inhibitory Peptide (ZIP) interferes with memory maintenance and long-term potentiation (LTP). However, mice lacking its putative target, the protein kinase PKMζ, exhibit normal learning and memory as well as LTP, making ZIP's mechanism unclear. Here, we show that ZIP disrupts LTP by removing surface AMPA receptors through its cationic charge alone. This effect was fully blocked by drugs that block macropinocytosis and is dependent on endophilin A2 (endoA2)-mediated endocytosis. ZIP and other cationic peptides selectively removed newly inserted AMPAR nanoclusters, providing a mechanism by which these peptides erase memories without effects on basal synaptic function. Lastly, cationic peptides can be administered locally and/or systemically and can be combined with local microinjection of macropinocytosis inhibitors to modulate memories on local and brain-wide scales. Our findings have critical implications for an entire field of memory mechanisms and highlight a previously unappreciated mechanism by which memories can be lost.
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PMID38045269
PMCPMC10690331
OpenAlexW4388849452
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