Pre-synaptic and post-synaptic neuronal activity supports the axon development of callosal projection neurons during different post-natal periods in the mouse cerebral cortex
Pre-synaptic and post-synaptic neuronal activity supports the axon development of callosal projection neurons during different post-natal periods in the mouse cerebral cortex
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DOI：
10.1111/j.1460-9568.2009.07070.x
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发表时间：
2010-02-01
影响因子：
3.4
通讯作者：
Tagawa, Yoshiaki
中科院分区：
文献类型：
--
作者：
Mizuno, Hidenobu;Hirano, Tomoo;Tagawa, Yoshiaki
胼胝体投射神经元是哺乳动物大脑皮层中主要的投射神经元类型之一，其轴突投射需要神经元的活动[H。Mizuno等人（2007）J. Neurosci.，27，6760-6770; C. L. Wang等人（2007）J. Neurosci.，27，11334-11342]。在这里，我们建立了一种方法来标记一些胼胝体轴突与增强的绿色荧光蛋白在小鼠大脑皮层和检查突触前/突触后神经元沉默对个别胼胝体轴突的形态学的影响。Kir2.1钾通道过表达使突触前/突触后神经元电沉默。单轴突追踪显示，到达皮质神经支配区后，绿色荧光蛋白标记的胼胝体轴突经历了连续的发育阶段：轴突生长，分支，层特异性靶向和乔木形成之间的出生后第5天（P）和P9，和随后的加工之间的P9和P15的轴突乔木。减少突触前神经元的活动扰乱轴突的生长和分支前P9，以及乔木加工之后。相反，沉默突触后神经元扰乱轴突乔木之间的P9和P15的阐述。因此，突触前神经元沉默比突触后神经元沉默显著影响更早阶段的胼胝体投射神经元轴突发育。沉默突触前和突触后神经元损害胼胝体轴突的预测，这表明，在突触前和突触后神经元的放电活动的某些水平是必要的胼胝体轴突的发展。我们的研究结果提供了体内证据，表明突触前和突触后神经元活动在皮质轴突发育期间的轴突生长、分支、乔木形成和发育中发挥着关键且可能是不同的作用。
Callosal projection neurons, one of the major types of projection neurons in the mammalian cerebral cortex, require neuronal activity for their axonal projections [H. Mizuno et al. (2007) J. Neurosci., 27, 6760-6770; C. L. Wang et al. (2007) J. Neurosci., 27, 11334-11342]. Here we established a method to label a few callosal axons with enhanced green fluorescent protein in the mouse cerebral cortex and examined the effect of pre-synaptic/post-synaptic neuron silencing on the morphology of individual callosal axons. Pre-synaptic/post-synaptic neurons were electrically silenced by Kir2.1 potassium channel overexpression. Single axon tracing showed that, after reaching the cortical innervation area, green fluorescent protein-labeled callosal axons underwent successive developmental stages: axon growth, branching, layer-specific targeting and arbor formation between post-natal day (P)5 and P9, and the subsequent elaboration of axon arbors between P9 and P15. Reducing pre-synaptic neuronal activity disturbed axon growth and branching before P9, as well as arbor elaboration afterwards. In contrast, silencing post-synaptic neurons disturbed axon arbor elaboration between P9 and P15. Thus, pre-synaptic neuron silencing affected significantly earlier stages of callosal projection neuron axon development than post-synaptic neuron silencing. Silencing both pre-synaptic and post-synaptic neurons impaired callosal axon projections, suggesting that certain levels of firing activity in pre-synaptic and post-synaptic neurons are required for callosal axon development. Our findings provide in-vivo evidence that pre-synaptic and post-synaptic neuronal activities play critical, and presumably differential, roles in axon growth, branching, arbor formation and elaboration during cortical axon development.