In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 29, No. 13 ( 2009-04-01), p. 4056-4064
Abstract:
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 (BDNF Met ) 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 BDNF Met 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 BDNF Met . BDNF Met mice were slower to extinguish an aversive CTA memory compared with wild-type counterparts. Moreover, the BDNF Met 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 BDNF Met 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.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.5539-08.2009
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2009
detail.hit.zdb_id:
1475274-8
SSG:
12
