Proximal and distal spinal neurons innervating multiple synergist and antagonist motor pools.

Proximal and distal spinal neurons innervating multiple synergist and antagonist motor pools.
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DOI:
10.7554/elife.70858
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发表时间:
2021-11-02
期刊:
影响因子:
7.7
通讯作者:
Beato M
Beato M
中科院分区:
生物学1区
文献类型:
--
作者:
Ronzano R;Lancelin C;Bhumbra GS;Brownstone RM;Beato M

文献摘要

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运动神经元(MN)控制肌肉收缩,它们通过前运动回路的募集来产生精确的运动行为。为了了解这些回路如何协调关节之间的运动,有必要了解突触前运动池的脊髓神经元是否对一个以上的MN群体有不同的投射。在这里,我们使用修改后的狂犬病病毒在小鼠中追踪调查前运动中间神经元投射到屈肌或伸肌MN,以及那些投射到拮抗剂对肌肉控制踝关节。我们发现,类似比例的前运动神经元分叉到运动池和拮抗剂。在整个脊髓中可以看到发散的运动前神经元,随着距离后肢增大,数量减少,但比例增加。在颈髓,分歧长下降propriospinal神经元被发现在对侧的第八层,有大的胞体,既不是甘氨酸,也不是胆碱能,并投射到腰椎和颈椎MN。我们的结论是,分布式脊髓运动前神经元协调活动跨多个运动池,并有脊髓神经元介导的拮抗肌的共同收缩。我们能够走路,跑步和以其他方式移动我们的身体,这要归功于脊髓中的神经元回路,这些神经元控制我们的肌肉如何以及何时收缩和放松。被称为前运动神经元的神经元从中枢神经系统的其他部分接收信息,并控制直接激活个体肌肉的运动神经元组(称为池)的活动。要弯曲关节或移动我们的四肢,需要协调不同肌肉的运动。以前的研究集中在前运动神经元如何激活运动神经元池来收缩单个肌肉,但目前尚不清楚这些前运动神经元中的一些是否以及如何共同激活不同的运动神经元池来同时控制多块肌肉。在这里,Ronzano,Lancelin等人给小鼠注射了用不同荧光标记物标记的改良狂犬病病毒,以建立运动前神经元的地图,这些神经元连接到控制腿部肌肉的运动神经元。实验显示,小鼠脊髓中的许多单个运动前神经元连接到不同的运动神经元池。在脊髓的上部区域(主要负责控制前腿),一些大的运动前神经元激活了该区域的运动神经元,以及脊髓下部区域(控制后腿)的其他运动神经元。这表明这些大的运动前神经元可能对协调肢体内和肢体之间的肌肉收缩很重要。许多神经系统疾病与肌肉收缩或放松困难有关。例如,患有肌张力障碍的人会经历无组织和过度的肌肉收缩,从而使他们无法正确地弯曲和伸直关节。通过帮助我们了解身体如何同时协调多个肢体的活动,Ronzano,Lancelin等人的发现可能会导致新的研究路线,最终改善肌张力障碍和其他类似神经系统疾病患者的生活质量。
Motoneurons (MNs) control muscle contractions, and their recruitment by premotor circuits is tuned to produce accurate motor behaviours. To understand how these circuits coordinate movement across and between joints, it is necessary to understand whether spinal neurons pre-synaptic to motor pools have divergent projections to more than one MN population. Here, we used modified rabies virus tracing in mice to investigate premotor interneurons projecting to synergist flexor or extensor MNs, as well as those projecting to antagonist pairs of muscles controlling the ankle joint. We show that similar proportions of premotor neurons diverge to synergist and antagonist motor pools. Divergent premotor neurons were seen throughout the spinal cord, with decreasing numbers but increasing proportion with distance from the hindlimb enlargement. In the cervical cord, divergent long descending propriospinal neurons were found in contralateral lamina VIII, had large somata, were neither glycinergic, nor cholinergic, and projected to both lumbar and cervical MNs. We conclude that distributed spinal premotor neurons coordinate activity across multiple motor pools and that there are spinal neurons mediating co-contraction of antagonist muscles. We are able to walk, run and move our bodies in other ways thanks to circuits of neurons in the spinal cord that control how and when our muscles contract and relax. Neurons known as premotor neurons receive information from other parts of the central nervous system and control the activities of groups (known as pools) of motor neurons that directly activate individual muscles. To bend a joint or move our limbs, the movement of different muscles needs to be coordinated. Previous studies have focused on how premotor neurons activate a pool of motor neurons to contract a single muscle, but it remains unclear if and how some of these premotor neurons can co-activate different pools of motor neurons to control more than one muscle at the same time. Here, Ronzano, Lancelin et al. injected mice with modified rabies viruses labelled with different fluorescent markers to build a map of the premotor neurons that connect to motor neurons controlling the leg muscles. The experiments revealed that many of the individual premotor neurons in the spinal cords of mice connected to different pools of motor neurons. In the upper region of the spinal cord – which is primarily responsible for controlling the front legs – some large premotor neurons activated motor neurons in this region as well as other motor neurons in a lower region of the spinal cord that controls the back legs. This suggests that these large premotor neurons may be important for coordinating muscles contraction within and between limbs. Many neurological diseases are associated with difficulties in contracting or relaxing muscles. For example, individuals with a condition called dystonia experience disorganized and excessive muscle contractions that prevent them from being able to bend and straighten their joints properly. By helping us to understand how the body coordinates the activities of multiple limbs at the same time, the findings of Ronzano, Lancelin et al. may lead to new lines of research that ultimately improve the quality of life of patients with dystonia and other similar neurological diseases.