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A decreased activation of the infralimbic medial prefrontal cortex (IL-mPFC), a brain region critical for the regulation of affective behaviors, has been described in BDNF<jats:sup>Met<\/jats:sup>carriers. However, it is unclear whether and how the Val66Met polymorphism affects the IL-mPFC synapses. Here, we report that spike timing-dependent plasticity (STDP) was absent in the IL-mPFC pyramidal neurons from BDNF<jats:sup>Met\/Met<\/jats:sup>mice, a mouse that recapitulates the specific phenotypic properties of the human BDNF Val66Met polymorphism. Also, we observed a decrease in NMDA and GABA receptor-mediated synaptic transmission in the pyramidal neurons of BDNF<jats:sup>Met\/Met<\/jats:sup>mice. While BDNF enhanced non-NMDA receptor transmission and depressed GABA receptor transmission in the wild-type mice, both effects were absent in BDNF<jats:sup>Met\/Met<\/jats:sup>mice after BDNF treatment. Indeed, exogenous BDNF reversed the deficits in STDP and NMDA receptor transmission in BDNF<jats:sup>Met\/Met<\/jats:sup>neurons. BDNF-mediated selective reversal of the deficit in plasticity and NMDA receptor transmission, but its lack of effect on GABA and non-NMDA receptor transmission in BDNF<jats:sup>Met\/Met<\/jats:sup>mice, suggests separate mechanisms of Val66Met polymorphism upon synaptic transmission. The effect of the Val66Met polymorphism on synaptic transmission and plasticity in the IL-mPFC represents a mechanism to account for this impact of SNP on affective disorders and cognitive dysfunction.<\/jats:p>","DOI":"10.1523\/jneurosci.5205-11.2012","type":"journal-article","created":{"date-parts":[[2012,2,14]],"date-time":"2012-02-14T17:25:39Z","timestamp":1329240339000},"page":"2410-2421","source":"Crossref","is-referenced-by-count":140,"title":["The BDNF Val66Met Polymorphism Impairs Synaptic Transmission and Plasticity in the Infralimbic Medial Prefrontal Cortex"],"prefix":"10.1523","volume":"32","author":[{"given":"Siobhan S.","family":"Pattwell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin 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