Gogolla Nadine, Galimberti Ivan, Deguchi Yuichi, Caroni Pico
Friedrich Miescher Institut, CH-4058 Basel, Switzerland.
Neuron. 2009 May 28;62(4):510-25. doi: 10.1016/j.neuron.2009.04.022.
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 Wnt 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 Wnt signaling.
我们研究了经验如何调节成年小鼠特定神经元回路的结构。丰富环境（EE）使海马透明层突触数量、苔藓纤维终末（LMT）数量以及LMT处的棘突加突触密度产生了强劲且可逆的增加，而一种依赖Rab3a的独特机制促进了LMT体积的增长。同时，EE增加了突触后CA3锥体神经元的Wnt7a/b水平。通过局部应用sFRP-1抑制Wnt信号传导，可抑制EE对突触数量的影响，并进一步减少对照小鼠的突触数量。应用于CA3的Wnt7模拟了EE对突触和LMT数量的影响。CA3的Wnt7a/b水平因兴奋性活动而增强，因sFRP-1而降低。突触数量和Wnt7a/b水平在6至12个月大的小鼠中达到峰值；老年小鼠中的下降通过EE得以逆转。因此，行为经验通过Wnt信号传导特异性地调节成年小鼠整体透明层突触数量和海马网络结构。
