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Here we show that LTP is impaired in hippocampal slices from presymptomatic<jats:italic>Hdh<\/jats:italic><jats:sup>Q92<\/jats:sup>and<jats:italic>Hdh<\/jats:italic><jats:sup>Q111<\/jats:sup>knock-in mice, describe two factors contributing to this deficit, and establish that potentiation can be rescued with brain-derived neurotrophic factor (BDNF). Baseline physiological measures were unaffected by the HD mutation, but LTP induction and, to a greater degree, consolidation were both defective. The facilitation of burst responses that normally occurs during a theta stimulation train was reduced in HD knock-in mice, as was theta-induced actin polymerization in dendritic spines. The decrease in actin polymerization and deficits in LTP stabilization were reversed by BDNF, concentrations of which were substantially reduced in hippocampus of both<jats:italic>Hdh<\/jats:italic><jats:sup>Q92<\/jats:sup>and<jats:italic>Hdh<\/jats:italic><jats:sup>Q111<\/jats:sup>mice. These results suggest that the HD mutation discretely disrupts processes needed to both induce and stabilize LTP, with the latter effect likely arising from reduced BDNF expression. That BDNF rescues LTP in HD knock-in mice suggests the possibility of treating cognitive deficits in asymptomatic HD gene carriers by upregulating production of the neurotrophin.<\/jats:p>","DOI":"10.1523\/jneurosci.5113-06.2007","type":"journal-article","created":{"date-parts":[[2007,4,18]],"date-time":"2007-04-18T16:48:03Z","timestamp":1176914883000},"page":"4424-4434","source":"Crossref","is-referenced-by-count":167,"title":["Brain-Derived Neurotrophic Factor Restores Synaptic Plasticity in a Knock-In Mouse Model of Huntington's Disease"],"prefix":"10.1523","volume":"27","author":[{"given":"Gary","family":"Lynch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eniko A.","family":"Kramar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher 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