Brain-derived neurotrophic factor and TrkB modulate visual experience-dependent refinement of neuronal pathways in retina
Brain-derived neurotrophic factor and TrkB modulate visual experience-dependent refinement of neuronal pathways in retina
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DOI：
10.1523/jneurosci.0779-07.2007
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发表时间：
2007-07-04
影响因子：
5.3
通讯作者：
Copenhagen, David R.
中科院分区：
文献类型：
--
作者：
Liu, Xiaorong;Grishanin, Ruslan N.;Copenhagen, David R.
感官体验完善了神经元的结构和功能。视觉系统已被证明是研究这种可塑性的有效模型系统。在新生儿视网膜中，很大一部分神经节细胞的树突状乔木弥漫性分布于内丛状层。随着成熟，许多这些乔木变成单层化的。视觉剥夺抑制了这种重塑。控制成熟和经验依赖的细化的分子机制所知甚少。在这里，我们测试了脑源性神经营养因子（BDNF）的假设，它调节大脑中的树突分支和突触功能，调节视网膜神经节细胞的发育和视觉经验依赖的细化。我们使用转基因小鼠系，用黄色荧光蛋白标记少量神经节细胞，来描绘它们在体内的树突结构。我们发现转基因BDNF的过表达加速了神经节细胞树突的层状细化，而TrkB表达的减少或视网膜特异性缺失TrkB （BDNF的同源受体）则延缓了这一过程。BDNF-TrkB信号调节ON细胞中新分支的成熟形成，但不调节双胺化的ON- off神经节细胞。此外，BDNF过表达超越了视觉输入刺激神经节细胞层流细化和树突状分支的要求。这些实验揭示了BDNF和TrkB在控制视觉系统中神经元结构的细胞特异性、经验依赖性重构中的先前未被认识的作用。
Sensory experience refines neuronal structure and functionality. The visual system has proved to be a productive model system to study this plasticity. In the neonatal retina, the dendritic arbors of a large proportion of ganglion cells are diffuse in the inner plexiform layer. With maturation, many of these arbors become monolaminated. Visual deprivation suppresses this remodeling. Little is known of the molecular mechanisms controlling maturational and experience-dependent refinement. Here, we tested the hypothesis that brain-derived neurotrophic factor ( BDNF), which is known to regulate dendritic branching and synaptic function in the brain, modulates the developmental and visual experience-dependent refinement of retinal ganglion cells. We used a transgenic mouse line, in which a small number of ganglion cells were labeled with yellow fluorescence protein, to delineate their dendritic structure in vivo. We found that transgenic overexpression of BDNF accelerated the laminar refinement of ganglion cell dendrites, whereas decreased TrkB expression or retina-specific deletion of TrkB, the cognate receptor for BDNF, retarded it. BDNF-TrkB signaling regulated the maturational formation of new branches in ON but not the bilaminated ON-OFF ganglion cells. Furthermore, BDNF overexpression overrides the requirement for visual inputs to stimulate laminar refinement and dendritic branching of ganglion cells. These experiments reveal a previously unrecognized action of BDNF and TrkB in controlling cell-specific, experience-dependent remodeling of neuronal structures in the visual system.