Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York, USA.
Nat Neurosci. 2012 Feb 5;15(3):399-405, S1. doi: 10.1038/nn.3042.
The sequential synaptic integration of adult-born neurons has been widely examined in rodents, but the mechanisms regulating the integration remain largely unknown. The primary cilium, a microtubule-based signaling center, is essential for vertebrate development, including the development of the CNS. We examined the assembly and function of the primary cilium in the synaptic integration of adult-born mouse hippocampal neurons. Primary cilia were absent in young adult-born neurons, but assembled precisely at the stage when newborn neurons approach their final destination, further extend dendrites and form synapses with entorhinal cortical projections. Conditional deletion of cilia from adult-born neurons induced severe defects in dendritic refinement and synapse formation. Deletion of primary cilia led to enhanced Wnt and β-catenin signaling, which may account for these developmental defects. Taken together, our findings identify the assembly of primary cilia as a critical regulatory event in the dendritic refinement and synaptic integration of adult-born neurons.
成年新生神经元的顺序性突触整合在啮齿动物中已经得到广泛研究，但调节整合的机制在很大程度上仍然未知。初级纤毛是一种基于微管的信号中心，对于脊椎动物的发育至关重要，包括中枢神经系统的发育。我们研究了初级纤毛在成年新生小鼠海马神经元突触整合中的组装和功能。年轻的成年新生神经元中没有初级纤毛，但在新生神经元接近最终目的地的阶段，它们精确地组装，进一步延伸树突并与内嗅皮层投射形成突触。从成年新生神经元中条件性删除纤毛会导致树突细化和突触形成的严重缺陷。初级纤毛的缺失导致 Wnt 和 β-连环蛋白信号的增强，这可能解释了这些发育缺陷。总之，我们的发现确定了初级纤毛的组装是成年新生神经元树突细化和突触整合的一个关键调节事件。
