Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain
Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain
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DOI：
10.1073/pnas.0806658105
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发表时间：
2008-09-16
影响因子：
11.1
通讯作者：
Cheng, Hwai-Jong
中科院分区：
文献类型：
--
作者：
Faulkner, Regina L.;Jang, Mi-Hyeon;Cheng, Hwai-Jong
成年哺乳动物大脑的有限区域不断产生新的神经元。尽管这些成年出生的神经元已经被证明接受突触输入，但对它们的突触输出知之甚少。用逆转录病毒介导的出生测定和标记结合连续切片电子显微镜重建，我们报道了成年出生的齿状颗粒细胞的苔藓纤维在出生后2周内与CA3锥体细胞形成初始突触，并于8周内在成年海马区达到形态成熟。在新生颗粒细胞中敲除精神分裂症中的中断-1(DISC1)会导致成年大脑中轴突靶向和突触输出的发育缺陷。再加上以前关于突触输入的报道，这些结果表明成年出生的神经元完全整合到现有的神经元电路中。我们的结果还表明DISC1在突触前发育中发挥了作用，并可能对精神分裂症和相关精神障碍的病因有一定的影响。
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.