Wang X, Berninger B, Poo M
Department of Biology, University of California at San Diego, La Jolla, California 92093-0357, USA.
J Neurosci. 1998 Jul 1;18(13):4985-92. doi: 10.1523/JNEUROSCI.18-13-04985.1998.
Neurotrophins secreted by the postsynaptic target cell may participate in activity-dependent synaptic modification during development and in the mature brain. A fundamental question of how neurotrophins can sculpt synaptic connections is whether neurotrophin-induced synaptic changes are spatially restricted to the site of neurotrophin secretion or whether they can spread to neighboring synapses. Using a model system of nerve-muscle coculture in which neurotrophin-4 (NT-4) is overexpressed in a subpopulation of postsynaptic myocytes, we demonstrated that presynaptic potentiation is restricted to synapses on myocytes overexpressing NT-4 without affecting nearby synapses formed by the same neuron on control myocytes. Likewise, postsynaptic modulation of acetylcholine channels by secreted NT-4 is spatially restricted to <60 micron from the site of NT-4 secretion. Therefore, activity-dependent secretion of neurotrophins can result in highly localized modification of neuronal connections.
由突触后靶细胞分泌的神经营养因子可能在发育过程以及成熟大脑中参与依赖活动的突触修饰。神经营养因子如何塑造突触连接这一基本问题在于，神经营养因子诱导的突触变化在空间上是局限于神经营养因子分泌位点，还是能够扩散到相邻突触。利用神经肌肉共培养模型系统，其中神经营养因子4（NT-4）在突触后肌细胞亚群中过表达，我们证明突触前增强局限于过表达NT-4的肌细胞上的突触，而不影响同一神经元在对照肌细胞上形成的附近突触。同样，分泌的NT-4对乙酰胆碱通道的突触后调节在空间上局限于距NT-4分泌位点<60微米的范围内。因此，神经营养因子的依赖活动分泌可导致神经元连接的高度局部修饰。
