Nagappan Guhan, Lu Bai
Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, National Institutes of Health, 35 Lincoln Drive, MSC 3714, Bethesda, MD 20892-4480, USA.
Trends Neurosci. 2005 Sep;28(9):464-71. doi: 10.1016/j.tins.2005.07.003.
Although brain-derived neurotrophic factor (BDNF) has emerged as a key regulator of activity-dependent synaptic plasticity, a conceptually challenging question is how this diffusible molecule achieves local and synapse-specific modulation. One hypothesis is that neuronal activity enhances BDNF signaling by selectively modulating TrkB receptors at active neurons or synapses without affecting receptors on neighboring, less-active ones. Growing evidence suggests that neuronal activity facilitates cell-surface expression of TrkB. BDNF secreted from active synapses and neurons recruits TrkB from extrasynaptic sites into lipid rafts, microdomains of membrane that are enriched at synapses. Postsynaptic rises in cAMP concentrations facilitate translocation of TrkB into the postsynaptic density. Finally, neuronal activity promotes BDNF-induced TrkB endocytosis, a signaling event important for many long-term BDNF functions. These mechanisms could collectively underlie synapse-specific regulation by BDNF.
尽管脑源性神经营养因子（BDNF）已成为活动依赖性突触可塑性的关键调节因子，但一个在概念上具有挑战性的问题是，这种可扩散分子如何实现局部和突触特异性调节。一种假说认为，神经元活动通过选择性调节活跃神经元或突触处的TrkB受体来增强BDNF信号传导，而不影响相邻活性较低的神经元上的受体。越来越多的证据表明，神经元活动促进TrkB的细胞表面表达。活跃突触和神经元分泌的BDNF将TrkB从突触外位点招募到脂筏中，脂筏是突触处富集的膜微区。突触后cAMP浓度的升高促进TrkB易位到突触后致密区。最后，神经元活动促进BDNF诱导的TrkB内吞作用，这是许多BDNF长期功能的重要信号事件。这些机制可能共同构成BDNF对突触特异性调节的基础。
