BRAIN-DERIVED NEUROTROPHIC FACTOR RAPIDLY ENHANCES SYNAPTIC TRANSMISSION IN HIPPOCAMPAL-NEURONS VIA POSTSYNAPTIC TYROSINE KINASE RECEPTORS
BRAIN-DERIVED NEUROTROPHIC FACTOR RAPIDLY ENHANCES SYNAPTIC TRANSMISSION IN HIPPOCAMPAL-NEURONS VIA POSTSYNAPTIC TYROSINE KINASE RECEPTORS
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DOI：
10.1073/pnas.92.17.8074
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发表时间：
1995-08-15
影响因子：
11.1
通讯作者：
PLUMMER, MR
中科院分区：
文献类型：
--
作者：
LEVINE, ES;DREYFUS, CF;PLUMMER, MR
尽管神经营养素主要与神经元存活和分化的长期影响有关，但最近的研究表明，也可以产生突触传递的急性变化。在与学习和记忆密切相关的海马体中，我们发现脑源性神经营养因子（BDNF）通过一种先前未报道的机制（通过磷酸化依赖性途径增加突触后反应性）快速增强突触功效。将 BDNF 应用到培养的海马神经元后几分钟内，自发放电率显着增加，兴奋性突触后电流的频率和幅度也显着增加。突触后电流频率的增加是由于突触前放电的变化所致。然而，增加的幅度起源于突触后，因为它被细胞内注射酪氨酸激酶受体 (Ntrk2/TrkB) 抑制剂 K-252a 选择性阻断，并通过注射磷酸酶抑制剂冈田酸增强。这些结果表明 BDNF 在海马突触传递的调节中发挥作用。
Although neurotrophins are primarily associated with long-term effects on neuronal survival and differentiation, recent studies have shown that acute changes in synaptic transmission can also be produced. In the hippocampus, an area critically involved in learning and memory, we have found that brain-derived neurotrophic factor (BDNF) rapidly enhanced synaptic efficacy through a previously unreported mechanism-increased postsynaptic responsiveness via a phosphorylation-dependent pathway. Within minutes of BDNF application to cultured hippocampal neurons, spontaneous firing rate was dramatically increased, as were the frequency and amplitude of excitatory postsynaptic currents. The increased frequency of postsynaptic currents resulted from the change in presynaptic firing. However, the increased amplitude was postsynaptic in origin because it was selectively blocked by intracellular injection of the tyrosine kinase receptor (Ntrk2/TrkB) inhibitor K-252a and potentiated by injection of the phosphatase inhibitor okadaic acid. These results suggest a role for BDNF in the modulation of synaptic transmission in the hippocampus.