Sequential development of synapses in dendritic domains during adult neurogenesis
Sequential development of synapses in dendritic domains during adult neurogenesis
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DOI：
10.1073/pnas.0807970105
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发表时间：
2008-10-28
影响因子：
11.1
通讯作者：
Lois, Carlos
中科院分区：
文献类型：
--
作者：
Kelsch, Wolfgang;Lin, Chia-Wei;Lois, Carlos
在整合到大脑回路的过程中，新的神经元与其适当的目标发展输入和输出突触。哺乳动物大脑中的绝大多数神经元是在出生前产生的，并在组装过程中整合到不成熟的回路中。相比之下，成人产生的神经元在整合成成熟的、功能齐全的回路时面临着额外的挑战。在这里，我们研究了单一神经元类型的突触，即嗅球中的颗粒细胞，在它们整合到新生大鼠的未成熟环路和成年大鼠的完全成熟环路期间是如何发育的。我们使用遗传学方法标记颗粒神经元中突触前和突触后的位置，并观察到突触在特定的树突域中的典型发育。在成体产生的神经元中，突触依次出现在不同的树状结构域中，谷氨酸能输入突触首先在近端树突域出现，几天后在远端区域出现输入输出突触，在基底域出现额外的输入突触。相反，对于新生动物产生的神经元，输入和输入输出突触分别同时出现在近端和远端区域，随后输入突触较晚出现在基底域。在成年出生的神经元中，突触的顺序形成，输入突触出现在输出突触之前，这可能代表了一种细胞机制，以最大限度地减少新神经元整合到成人大脑成熟回路中所造成的干扰。
During the process of integration into brain circuits, new neurons develop both input and output synapses with their appropriate targets. The vast majority of neurons in the mammalian brain are generated before birth and integrate into immature circuits while these are being assembled. In contrast, adult-generated neurons face an additional challenge as they integrate into a mature, fully functional circuit. Here, we examined how synapses of a single neuronal type, the granule cell in the olfactory bulb, develop during their integration into the immature circuit of the newborn and the fully mature circuit of the adult rat. We used a genetic method to label pre and postsynaptic sites in granule neurons and observed a stereotypical development of synapses in specific dendritic domains. In adult-generated neurons, synapses appeared sequentially in different dendritic domains with glutamatergic input synapses that developed first at the proximal dendritic domain, followed several days later by the development of input-output synapses in the distal domain and additional input synapses in the basal domain. In contrast, for neurons generated in neonatal animals, input and input-output synapses appeared simultaneously in the proximal and distal domains, respectively, followed by the later appearance of input synapses to the basal domain. The sequential formation of synapses in adult-born neurons, with input synapses appearing before output synapses, may represent a cellular mechanism to minimize the disruption caused by the integration of new neurons into a mature circuit in the adult brain.