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.2005.09.005
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发表时间：
2005-10-06
期刊：
影响因子：
16.2
通讯作者：
Kandell, ER
中科院分区：
文献类型：
--
作者：
Barco, A;Patterson, S;Kandell, ER
VP 16-CREB，CREB的组成型活性形式，在海马神经元的CA 1区的表达降低了阈值，引发晚期，持续阶段的长时程增强（L-LTP）在Schaffer侧支通路。这种VP 16-CREB介导的L-LTP与传统的LTP晚期不同，不依赖于新的转录。这一发现表明，在转基因小鼠中，编码这种形式的L-LTP所必需的蛋白质的mRNA转录本可能已经存在于基础条件下的CA 1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，我们探讨了我们的筛选揭示的最突出的候选基因，即前强啡肽，BDNF和MHC I类分子，促进VP 16-CREB小鼠的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 highdensity 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, namely prodynorphin, 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.