Gene Expression Profiling of Facilitated L-LTP in VP16-CREB Mice Reveals that BDNF Is Critical for the Maintenance of LTP and Its Synaptic Capture
Gene Expression Profiling of Facilitated L-LTP in VP16-CREB Mice Reveals that BDNF Is Critical for the Maintenance of LTP and Its Synaptic Capture
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DOI：
10.1016/j.neuron.2011.02.035
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发表时间：
2011-03
期刊：
影响因子：
16.2
通讯作者：
A. Barco;S. Patterson;J. Alarcon;Petra Gromova;Manuel Mata-Roig;Alexei Morozov;E. Kandel
中科院分区：
文献类型：
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作者：
A. Barco;S. Patterson;J. Alarcon;Petra Gromova;Manuel Mata-Roig;Alexei Morozov;E. Kandel
VP16-CREB（CREB 的一种组成型活性形式）在 CA1 区海马神经元中的表达降低了在 Schaffer 侧支通路中引发长时程增强 (L-LTP) 晚期持续期 (L-LTP) 的阈值。这种 VP16-CREB 介导的 L-LTP 与传统的 LTP 晚期阶段不同，不依赖于新的转录。这一发现表明，在转基因小鼠中，编码这种 L-LTP 形式所需蛋白质的 mRNA 转录物可能已经存在于基础条件下的 CA1 神经元中。我们使用高密度寡核苷酸阵列来鉴定转基因小鼠和野生型小鼠海马中差异表达的 mRNA。然后，我们探讨了筛选中揭示的最突出的候选基因，即强啡肽原、BDNF 和 MHC I 类分子，对 VP16-CREB 小鼠的促进 LTP 的贡献。我们发现脑源性神经营养因子的过度表达是这种表型的重要组成部分。
Expression of VP16-CREB, a constitutively active form of CREB, in hippocampal neurons of the CA1 region lowers the threshold for eliciting the late, persistent phase of long-term potentiation (L-LTP) in the Schaffer collateral pathway. This VP16-CREB-mediated L-LTP differs from the conventional late phase of LTP in not being dependent on new transcription. This finding suggests that in the transgenic mice the mRNA transcript(s) encoding the protein(s) necessary for this form of L-LTP might already be present in CA1 neurons in the basal condition. We used high-density oligonucleotide arrays to identify the mRNAs differentially expressed in the hippocampus of transgenic and wild-type mice. We then explored the contribution of the most prominent candidate genes revealed by our screening, namelyprodynorphin,BDNF, and MHC class I molecules, to the facilitated LTP of VP16-CREB mice. We found that the overexpression of brain-derived neurotrophic factor accounts for an important component of this phenotype.