Wnt Signaling Mediates Experience-Related Regulation of Synapse Numbers and Mossy Fiber Connectivities in the Adult Hippocampus
Wnt Signaling Mediates Experience-Related Regulation of Synapse Numbers and Mossy Fiber Connectivities in the Adult Hippocampus
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DOI：
10.1016/j.neuron.2009.04.022
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发表时间：
2009-05-28
期刊：
影响因子：
16.2
通讯作者：
Caroni, Pico
中科院分区：
文献类型：
--
作者：
Gogolla, Nadine;Galimberti, Ivan;Caroni, Pico
我们研究了经验如何调节成年小鼠神经元回路的结构。丰富的环境（EE）产生了一个强大的和可逆的增加海马透明层突触的数量，苔藓纤维终端（LMT）的数量，和脊柱加突触密度在LMT，而一个独特的机制，依赖于Rab 3a促进LMT体积的增长。与此同时，EE增加突触后CA 3锥体神经元Wnt 7a/B水平。通过局部应用sFRP-1抑制Writ信号传导抑制了EE对突触数量的影响，并进一步减少了对照小鼠的突触数量。应用于CA 3的Wnt 7模拟EE对突触和LMT数量的影响。CA 3 Wnt 7a/B水平通过兴奋性活动增强，并通过sFRP-1降低。突触数量和Wnt 7a/B水平在6-12月龄小鼠中达到峰值;老年小鼠的下降被EE逆转。因此，行为经验通过Writ信号特异性地调节成年全球透明层突触数量和海马网络结构。
We investigated how experience regulates the structure of a defined neuronal circuit in adult mice. Enriched environment (EE) produced a robust and reversible increase in hippocampal stratum lucidum synapse numbers, mossy fiber terminal (LMT) numbers, and spine plus synapse densities at LMTs, whereas a distinct mechanism depending on Rab3a promoted LMT volume growth. In parallel, EE increased postsynaptic CA3 pyramidal neuron Wnt7a/b levels. Inhibiting Writ signaling through locally applied sFRP-1 suppressed the effects of EE on synapse numbers and further reduced synapse numbers in control mice. Wnt7 applied to CA3 mimicked the effects of EE on synapse and LMT numbers. CA3 Wnt7a/b levels were enhanced by excitatory activity and reduced by sFRP-1. Synapse numbers and Wnt7a/b levels peaked in mice aged 6-12 months; a decline in aged mice was reversed by EE. Therefore, behavioral experience specifically regulates adult global stratum lucidum synapse numbers and hippocampal network structure through Writ signaling.