{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:48:00Z","timestamp":1791283680895,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"45","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,11,8]]},"abstract":"<jats:p>Long-term memory (LTM) formation has been linked with functional strengthening of existing synapses and other processes including de novo synaptogenesis. However, it is unclear whether synaptogenesis can contribute to LTM formation. Here, using \u03b1-calcium\/calmodulin kinase II autophosphorylation-deficient (T286A) mutants, we demonstrate that when functional strengthening is severely impaired, contextual LTM formation is linked with training-induced PSD95 up-regulation followed by persistent generation of multiinnervated spines, a type of synapse that is characterized by several presynaptic terminals contacting the same postsynaptic spine. Both PSD95 up-regulation and contextual LTM formation in T286A mutants required signaling by the mammalian target of rapamycin (mTOR). Furthermore, we show that contextual LTM resists destabilization in T286A mutants, indicating that LTM is less flexible when synaptic strengthening is impaired. Taken together, we suggest that activation of mTOR signaling, followed by overexpression of PSD95 protein and synaptogenesis, contributes to formation of invariant LTM when functional strengthening is impaired.<\/jats:p>","DOI":"10.1073\/pnas.1109680108","type":"journal-article","created":{"date-parts":[[2011,10,25]],"date-time":"2011-10-25T01:52:20Z","timestamp":1319507540000},"page":"18471-18475","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":92,"title":["Mechanism for long-term memory formation when synaptic strengthening is impaired"],"prefix":"10.1073","volume":"108","author":[{"given":"Kasia","family":"Radwanska","sequence":"first","affiliation":[{"name":"Institute of Psychiatry, King's College London, London SE5 9NU, United Kingdom;"},{"name":"Department of Molecular and Cellular Neuroscience, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland;"},{"name":"Department of Pharmacology, Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay I.","family":"Medvedev","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, The Open University, Milton Keynes MK7 6AA, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace S.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, King's College London, London SE5 9NU, United Kingdom;"},{"name":"Neuroscience Centre, Department of Physiology and Biophysics, Federal University of Minas Gerais, 31270-901 Belo Horizonte, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Engmann","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, King's College London, London SE5 9NU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Thiede","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, King's College London, London SE5 9NU, United Kingdom;"},{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcio F. D.","family":"Moraes","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, King's College London, London SE5 9NU, United Kingdom;"},{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Villers","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of Mons, 7000 Mons, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine E.","family":"Irvine","sequence":"additional","affiliation":[{"name":"Centre for Diabetes and Endocrinology, Rayne Institute, University College London, London WC1E 6JJ, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicollette S.","family":"Maunganidze","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, King's College London, London SE5 9NU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta M.","family":"Pyza","sequence":"additional","affiliation":[{"name":"Institute of Zoology, Jagiellonian University, 30-060 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Ris","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of Mons, 7000 Mons, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"Szyma\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neuroscience, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Lipi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neuroscience, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leszek","family":"Kaczmarek","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neuroscience, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, The Open University, Milton Keynes MK7 6AA, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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