The BDNF Val66Met Polymorphism Impairs Synaptic Transmission and Plasticity in the Infralimbic Medial Prefrontal Cortex

被引:123
作者
Pattwell, Siobhan S. [2 ]
Bath, Kevin G. [3 ]
Perez-Castro, Rosalia [4 ]
Lee, Francis S. [2 ]
Chao, Moses V. [4 ]
Ninan, Ipe [1 ]
机构
[1] NYU, Sch Med, Dept Psychiat, Langone Med Ctr, 540 1st Ave, New York, NY 10016 USA
[2] Cornell Univ, Weill Cornell Med Coll, Dept Psychiat, New York, NY 10065 USA
[3] Brown Univ, Dept Neurosci, Providence, RI 02912 USA
[4] NYU, Sch Med, Mol Neurobiol Program, Skirball Inst, New York, NY 10016 USA
关键词
CULTURED HIPPOCAMPAL-NEURONS; POSTTRAUMATIC-STRESS-DISORDER; TIMING-DEPENDENT PLASTICITY; LONG-TERM POTENTIATION; CL-COTRANSPORTER KCC2; NEUROTROPHIC FACTOR; FEAR EXTINCTION; DEPRESSED-PATIENTS; CONDITIONED FEAR; NMDA RECEPTORS;
D O I
10.1523/JNEUROSCI.5205-11.2012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The brain-derived neurotrophic factor (BDNF) Va166Met polymorphism is a common human single nucleotide polymorphism (SNP) that affects the regulated release of BDNF, and has been implicated in affective disorders and cognitive dysfunction. 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 BDNFMet carriers. However, it is unclear whether and how the Va166Met polymorphism affects the IL-mPFC synapses. Here, we report that spike timing-dependent plasticity (STDP) was absent in the IL-mPFC pyramidal neurons from BDNFMet/Met mice, a mouse that recapitulates the specific phenotypic properties of the human BDNF Va166Met polymorphism. Also, we observed a decrease in NMDA and GABA receptor-mediated synaptic transmission in the pyramidal neurons of BDNFMet/Met mice. While BDNF enhanced non-NMDA receptor transmission and depressed GABA receptor transmission in the wild-type mice, both effects were absent in BDNFMet/Met mice after BDNF treatment. Indeed, exogenous BDNF reversed the deficits in STDP and NMDA receptor transmission in BDNFMet/Met 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 BDNFMet/Met mice, suggests separate mechanisms of Va166Met polymorphism upon synaptic transmission. The effect of the Va166Met 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.
引用
收藏
页码:2410 / 2421
页数:12
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