TY - JOUR T1 - Variant BDNF Val66Met Polymorphism Affects Extinction of Conditioned Aversive Memory JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4056 LP - 4064 DO - 10.1523/JNEUROSCI.5539-08.2009 VL - 29 IS - 13 AU - Hui Yu AU - Yue Wang AU - Siobhan Pattwell AU - Deqiang Jing AU - Ting Liu AU - Yun Zhang AU - Kevin G. Bath AU - Francis S. Lee AU - Zhe-Yu Chen Y1 - 2009/04/01 UR - http://www.jneurosci.org/content/29/13/4056.abstract N2 - Brain-derived neurotrophic factor (BDNF) plays important roles in activity-dependent plasticity processes, such as long-term potentiation, learning, and memory. The recently reported human BDNF Val66Met (BDNFMet) polymorphism has been shown to lead to altered hippocampal volume and impaired hippocampal-dependent memory and is associated with a variety of neuropsychiatric disorders. There are few studies, however, that investigate the effect of the BDNFMet polymorphism on hippocampal-independent memory processes. A conditioned taste aversion (CTA) task was used for studying the mechanisms of long-term, hippocampal-independent, nondeclarative memory in the mammalian brain. Using the CTA paradigm, we found a novel impairment in extinction learning, but not acquisition or retention, of aversive memories resulting from the variant BDNFMet. BDNFMet mice were slower to extinguish an aversive CTA memory compared with wild-type counterparts. Moreover, the BDNFMet was associated with smaller volume and decreased neuronal dendritic complexity in the ventromedial prefrontal cortex (vmPFC), which plays a significant role in extinction of CTA. Finally, this delay in extinction learning could be rescued pharmacologically with a cognitive enhancer, d-cycloserine (DCS). To our knowledge, this is the first evidence that the BDNFMet polymorphism contributes to abnormalities in memory extinction. This abnormality in extinction learning may be explained by alterations in neuronal morphology, as well as decreased neural activity in the vmPFC. Importantly, DCS was effective in rescuing this delay in extinction, suggesting that when coupled with behavior therapy, DCS may be an effective treatment option for anxiety disorders in humans with this genetic variant BDNF. ER -