Competition with Primary Sensory Afferents Drives Remodeling of Corticospinal Axons in Mature Spinal Motor Circuits
Competition with Primary Sensory Afferents Drives Remodeling of Corticospinal Axons in Mature Spinal Motor Circuits
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DOI：
10.1523/jneurosci.3441-15.2016
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发表时间：
2016-01-06
影响因子：
5.3
通讯作者：
Martin, John H.
中科院分区：
文献类型：
--
作者：
Jiang, Yu-Qiu;Zaaimi, Boubker;Martin, John H.
对成熟运动系统的损伤驱动显著的自发轴突发芽而不是轴突再生。了解轴突发芽的回路水平决定因素对于损伤后修复运动回路以实现功能康复是重要的。已知竞争性相互作用在发育过程中塑造皮质脊髓束轴突的生长和撤回。竞争是否以及如何促进成熟脊髓运动回路的重组尚不清楚。为了研究这个问题，我们研究了皮质脊髓轴突的可塑性变化，以响应两种互补的本体感受传入操作：（1）通过电刺激增强本体感受传入活动;或（2）通过背根切断术减少其输入。实验在成年大鼠中进行。电刺激产生本体感觉传入萌芽，伴随着显着的皮质脊髓轴突撤回和减少皮质脊髓连接胆碱能中间神经元的内侧中间带和运动神经元上的C扣。相反，背根切断导致皮质脊髓连接，包括胆碱能中间神经元的显着增加; C bouton密度相应增加。运动皮层诱发的肌肉电位表现出平行的皮质脊髓轴突的变化，这表明相互皮质脊髓轴突的变化是功能性的。使用这两个互补的模型，我们发现，竞争性的相互作用之间的本体感受和皮质脊髓轴突的组织成熟的皮质脊髓轴突和脊髓运动回路的一个重要的决定因素。竞争的活性和突触空间依赖性使得能够预测损伤后备用皮质脊髓连接和脊髓运动回路的重塑，并通知皮质脊髓连接的靶向特异性控制以促进功能恢复。
Injury to the mature motor system drives significant spontaneous axonal sprouting instead of axon regeneration. Knowing the circuit-level determinants of axonal sprouting is important for repairing motor circuits after injury to achieve functional rehabilitation. Competitive interactions are known to shape corticospinal tract axon outgrowth and withdrawal during development. Whether and how competition contributes to reorganization of mature spinal motor circuits is unclear. To study this question, we examined plastic changes in corticospinal axons in response to two complementary proprioceptive afferent manipulations: (1) enhancing proprioceptive afferents activity by electrical stimulation; or (2) diminishing their input by dorsal rootlet rhizotomy. Experiments were conducted in adult rats. Electrical stimulation produced proprioceptive afferent sprouting that was accompanied by significant corticospinal axon withdrawal and a decrease in corticospinal connections on cholinergic interneurons in the medial intermediate zone and C boutons on motoneurons. In contrast, dorsal rootlet rhizotomy led to a significant increase in corticospinal connections, including those on cholinergic interneurons; C bouton density increased correspondingly. Motor cortex-evoked muscle potentials showed parallel changes to those of corticospinal axons, suggesting that reciprocal corticospinal axon changes are functional. Using the two complementary models, we showed that competitive interactions between proprioceptive and corticospinal axons are an important determinant in the organization of mature corticospinal axons and spinal motor circuits. The activity- and synaptic space-dependent properties of the competition enables prediction of the remodeling of spared corticospinal connection and spinal motor circuits after injury and informs the target-specific control of corticospinal connections to promote functional recovery.