{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:20:15Z","timestamp":1791048015061,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T00:00:00Z","timestamp":1145577600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cognitive decline in Alzheimer's disease (AD) stems from the progressive dysfunction of synaptic connections within cortical neuronal microcircuits. Recently, soluble amyloid \u03b2 protein oligomers (A\u03b2<jats:sub>ol<\/jats:sub>s) have been identified as critical triggers for early synaptic disorganization. However, it remains unknown whether a deficit of Hebbian\u2010related synaptic plasticity occurs during the early phase of AD. Therefore, we studied whether age\u2010dependent A\u03b2 accumulation affects the induction of spike\u2010timing\u2010dependent synaptic potentiation at excitatory synapses on neocortical layer 2\/3 (L2\/3) pyramidal cells in the APPswe\/PS1dE9 transgenic mouse model of AD. Synaptic potentiation at excitatory synapses onto L2\/3 pyramidal cells was significantly reduced at the onset of A\u03b2 pathology and was virtually absent in mice with advanced A\u03b2 burden. A decreased \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazole propionate (AMPA)\/<jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate (NMDA) receptor\u2010mediated current ratio implicated postsynaptic mechanisms underlying A\u03b2 synaptotoxicity. The integral role of A\u03b2<jats:sub>ol<\/jats:sub>s in these processes was verified by showing that pretreatment of cortical slices with A\u03b2<jats:sub>(25\u221235)ol<\/jats:sub>s disrupted spike\u2010timing\u2010dependent synaptic potentiation at unitary connections between L2\/3 pyramidal cells, and reduced the amplitude of miniature excitatory postsynaptic currents therein. A robust decrement of AMPA, but not NMDA, receptor\u2010mediated currents in nucleated patches from L2\/3 pyramidal cells confirmed that A\u03b2<jats:sub>ol<\/jats:sub>s perturb basal glutamatergic synaptic transmission by affecting postsynaptic AMPA receptors. Inhibition of AMPA receptor desensitization by cyclothiazide significantly increased the amplitude of excitatory postsynaptic potentials evoked by afferent stimulation, and rescued synaptic plasticity even in mice with pronounced A\u03b2 pathology. We propose that soluble A\u03b2<jats:sub>ol<\/jats:sub>s trigger the diminution of synaptic plasticity in neocortical pyramidal cell networks during early stages of AD pathogenesis by preferentially targeting postsynaptic AMPA receptors.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2006.04733.x","type":"journal-article","created":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T11:39:35Z","timestamp":1145619575000},"page":"2035-2047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Non\u2010fibrillar \u03b2\u2010amyloid abates spike\u2010timing\u2010dependent synaptic potentiation at excitatory synapses in layer 2\/3 of the neocortex by targeting postsynaptic AMPA receptors"],"prefix":"10.1111","volume":"23","author":[{"given":"Isaac","family":"Shemer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Holmgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogier","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"F\u00fcl\u00f6p","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha","family":"Zilberter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle M.","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Farkas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"H\u00e4rtig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Botond","family":"Penke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nail","family":"Burnashev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Tanila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Zilberter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"Harkany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,4,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00051-J"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)03176-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-24-10464.1998"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/361031a0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1047-8477(02)00625-1"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1534900100"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/6374"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/nlme.2001.4034"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019417"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410270502"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.3269"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0285"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00008-8"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00992.2002"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/416433a"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03366"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.09.024"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902590305"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.11.011"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02898.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4884-03.2004"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1998.0230"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(97)00091-0"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00139.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1997.6581"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh019"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00124-7"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-02-00372.2001"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-04-01327.2001"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1234"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3432-04.2004"},{"key":"e_1_2_7_33_1","volume-title":"Practical Statistics for Non\u2010Mathematical People","author":"Langley R.","year":"1968"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.12.5734"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp022031"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5297.213"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(03)00128-3"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8918"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:NEUR.0000044197.83514.64"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00070.2003"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00434-3"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64010253.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn719"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4342-04.2005"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00576.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3034-05.2005"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2004.06.020"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.10.022"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81025-9"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1104-1054"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00542-6"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00476-8"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/35086072"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1503"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1515\/REVNEURO.2004.15.4.267"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.23.11158"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00275-6"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4386-03.2004"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1667"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300410"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20101"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90066-Z"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1335"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/416535a"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.09.010"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0233-04.2004"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1633-03.2004"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1999.81.2.781"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-9961(02)00009-8"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/25665"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00485.2004"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2004.05.006"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.04.037"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1460-9568.2006.04733.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1460-9568.2006.04733.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T16:30:19Z","timestamp":1696869019000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1460-9568.2006.04733.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,4]]},"references-count":72,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2006,4]]}},"alternative-id":["10.1111\/j.1460-9568.2006.04733.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1460-9568.2006.04733.x","archive":["Portico"],"relation":{},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,4]]},"assertion":[{"value":"2006-04-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}