Faulkner Regina L, Jang Mi-Hyeon, Liu Xiao-Bo, Duan Xin, Sailor Kurt A, Kim Ju Young, Ge Shaoyu, Jones Edward G, Ming Guo-li, Song Hongjun, Cheng Hwai-Jong
Center for Neuroscience, University of California, Davis, CA 95618, USA.
Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14157-62. doi: 10.1073/pnas.0806658105. Epub 2008 Sep 9.
New neurons are continuously generated in restricted regions of the adult mammalian brain. Although these adult-born neurons have been shown to receive synaptic inputs, little is known about their synaptic outputs. Using retrovirus-mediated birth-dating and labeling in combination with serial section electron microscopic reconstruction, we report that mossy fiber en passant boutons of adult-born dentate granule cells form initial synaptic contacts with CA3 pyramidal cells within 2 weeks after their birth and reach morphologic maturity within 8 weeks in the adult hippocampus. Knockdown of Disrupted-in-Schizophrenia-1 (DISC1) in newborn granule cells leads to defects in axonal targeting and development of synaptic outputs in the adult brain. Together with previous reports of synaptic inputs, these results demonstrate that adult-born neurons are fully integrated into the existing neuronal circuitry. Our results also indicate a role for DISC1 in presynaptic development and may have implications for the etiology of schizophrenia and related mental disorders.
成年哺乳动物大脑的特定区域会持续产生新的神经元。尽管这些成年新生神经元已被证明能接受突触输入，但对其突触输出却知之甚少。我们通过逆转录病毒介导的出生时间标记和标记技术，结合连续切片电子显微镜重建方法，报告称成年新生齿状颗粒细胞的苔藓纤维旁支在出生后2周内与CA3锥体细胞形成初始突触联系，并在成年海马体中8周内达到形态成熟。新生颗粒细胞中精神分裂症相关破坏蛋白1（DISC1）的敲低会导致成年大脑中轴突靶向和突触输出发育缺陷。结合先前关于突触输入的报道，这些结果表明成年新生神经元已完全整合到现有的神经元回路中。我们的结果还表明DISC1在突触前发育中发挥作用，这可能对精神分裂症及相关精神障碍的病因学具有启示意义。
