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We have used rats that are heterozygous for an autosomal\u2010dominant germline mutation in the TSC2 gene (TSC2<jats:sup>+\/\u2013<\/jats:sup> rats) to examine the consequences of TSC2 mutations for hippocampal synaptic plasticity. While basal synaptic transmission in the Schaffer collateral\u2013CA1 synapse was not altered, paired\u2010pulse plasticity was significantly enhanced in TSC2<jats:sup>+\/\u2013<\/jats:sup> rats (interpulse intervals 20\u2013200\u2003ms). Moreover, TSC2<jats:sup>+\/\u2013<\/jats:sup> rats exhibited a marked reduction of different forms of synaptic plasticity. Long\u2010term potentiation (LTP) elicited following high\u2010frequency tetanization of Schaffer collaterals was significantly decreased from 1.45\u2003\u00b1\u20030.05\u2010fold potentiation to 1.15\u2003\u00b1\u20030.04 (measured after 60\u2003min). This difference in LTP levels between TSC2<jats:sup>+\/\u2013<\/jats:sup> and wild\u2010type rats also persisted in the presence of the \u03b3\u2010aminobutyric acid (GABA)<jats:sub>A<\/jats:sub> receptor antagonist bicuculline. In addition to changed LTP, the level of long\u2010term depression (LTD) elicited by different forms of low\u2010frequency stimulation was significantly less in TSC2<jats:sup>+\/\u2013<\/jats:sup> rats. These results suggest that TSC2 mutations may cause hippocampal synapses to lose much of their potential for activity\u2010dependent synaptic modification. An understanding of the underlying molecular pathways may suggest new therapeutic approaches aimed at inhibiting the development of the profound mental retardation in TSC.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2006.04594.x","type":"journal-article","created":{"date-parts":[[2006,1,17]],"date-time":"2006-01-17T19:18:35Z","timestamp":1137525515000},"page":"686-692","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Impaired synaptic plasticity in a rat model of tuberous sclerosis"],"prefix":"10.1111","volume":"23","author":[{"given":"Christian","family":"Von Der Brelie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Waltereit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Kirschstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,2,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-22-08695.1997"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20211"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2004.04.009"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"7080","DOI":"10.1523\/JNEUROSCI.20-18-07080.2000","article-title":"Synaptic plasticity in the human dentate gyrus","volume":"20","author":"Beck H.","year":"2000","journal-title":"J. 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