Yoshii Akira, Constantine-Paton Martha
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139-4307, USA.
Nat Neurosci. 2007 Jun;10(6):702-11. doi: 10.1038/nn1903. Epub 2007 May 21.
The N-methyl-D-aspartate receptor (NMDAR), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95) and phosphatidylinositol 3-kinase (PI3K) have all been implicated in long-term potentiation. Here we show that these molecules are involved in a single pathway for synaptic potentiation. In visual cortical neurons in young rodents, the neurotrophin receptor TrkB is associated with PSD-95. When BDNF is applied to cultured visual cortical neurons, PSD-95-labeled synaptic puncta enlarge, and fluorescent recovery after photobleaching (FRAP) reveals increased delivery of green fluorescent protein-tagged PSD-95 to the dendrites. The recovery of fluorescence requires TrkB, signaling through PI3K and the serine-threonine kinase Akt, and an intact Golgi apparatus. Stimulation of NMDARs mimics the PSD-95 trafficking that is induced by BDNF but requires active BDNF and PI3K. Furthermore, local dendritic contact with a BDNF-coated microsphere induces PSD-95 FRAP throughout the dendrites of the stimulated neuron, suggesting that this mechanism induces rapid neuron-wide synaptic increases in PSD-95 and refinement whenever a few robust inputs activate the NMDAR-BDNF-PI3K pathway.
N-甲基-D-天冬氨酸受体（NMDAR）、脑源性神经营养因子（BDNF）、突触后致密蛋白95（PSD-95）和磷脂酰肌醇3激酶（PI3K）均与长时程增强作用有关。在此我们表明，这些分子参与了突触增强的单一途径。在幼龄啮齿动物的视觉皮层神经元中，神经营养因子受体TrkB与PSD-95相关联。当将BDNF应用于培养的视觉皮层神经元时，PSD-95标记的突触小体增大，光漂白后的荧光恢复（FRAP）显示绿色荧光蛋白标记的PSD-95向树突的递送增加。荧光的恢复需要TrkB、通过PI3K和丝氨酸-苏氨酸激酶Akt进行信号传导，以及完整的高尔基体。NMDAR的激活模拟了由BDNF诱导的PSD-95转运，但需要活性BDNF和PI3K。此外，与包被有BDNF的微球的局部树突接触会在受刺激神经元的整个树突中诱导PSD-95的FRAP，这表明每当一些强烈的输入激活NMDAR-BDNF-PI3K途径时，这种机制就会诱导PSD-95在全神经元范围内快速增加并实现精细化。
