Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition.

Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition.
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DOI:
10.1038/nature08000
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发表时间:
2009-06-11
期刊:
影响因子:
64.8
通讯作者:
Arber, Silvia
Arber, Silvia
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Pecho-Vrieseling, Eline;Sigrist, Markus;Yoshida, Yutaka;Jessell, Thomas M.;Arber, Silvia

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脊髓反射由感觉传入神经和运动神经元之间的突触连接介导。这些电路的组织表现出几个层次的特异性。只有某些类别的本体感觉神经元与运动神经元建立直接的单突触连接。那些这样做的人受到运动池特异性规则的约束-他们与提供相同肌肉的运动神经元形成强有力的连接,但避免提供拮抗肌肉的运动池。这种连接模式最初是准确的,并在没有活动的情况下保持,这意味着布线特异性依赖于感觉和运动神经元表面上识别分子的匹配。但是,与中枢神经系统(CNS)的大多数区域一样,这里精细突触特异性的决定因素尚未被定义。为了解决这些反射回路中突触特异性的起源,我们使用分子遗传学方法来操纵感觉和运动神经元亚群表达的识别蛋白。在这里,我们表明,识别系统,涉及所选运动神经元池的Sema 3e的表达,其高亲和力受体PlexinD 1的本体感觉神经元,是一个关键的决定因素,在感觉运动电路的突触特异性。改变感觉或运动神经元中的Sema 3e-PlexinD 1信号传导的概况导致单突触连接的功能和解剖学重新布线,但不改变运动池特异性。我们的研究结果表明,这种原型中枢神经系统回路中的单突触连接模式是通过基于排斥信号的识别程序构建的。
Spinal reflexes are mediated by synaptic connections between sensory afferents and motor neurons. The organization of these circuits exhibits several levels of specificity. Only certain classes of proprioceptive sensory neurons make direct, monosynaptic, connections with motor neurons. Those that do are bound by rules of motor pool specificity – they form strong connections with motor neurons supplying the same muscle, but avoid motor pools supplying antagonistic muscles. This pattern of connectivity is initially accurate and is maintained in the absence of activity, implying that wiring specificity relies on the matching of recognition molecules on the surface of sensory and motor neurons. But determinants of fine synaptic specificity here, as in most regions of the central nervous system (CNS), have yet to be defined. To address the origins of synaptic specificity in these reflex circuits we have used molecular genetic methods to manipulate recognition proteins expressed by subsets of sensory and motor neurons. We show here that a recognition system involving expression of Sema3e by selected motor neuron pools, and its high-affinity receptor PlexinD1 by proprioceptive sensory neurons, is a critical determinant of synaptic specificity in sensory-motor circuits. Changing the profile of Sema3e-PlexinD1 signaling in sensory or motor neurons results in functional and anatomical rewiring of monosynaptic connections, but does not alter motor pool specificity. Our findings indicate that patterns of monosynaptic connectivity in this prototypic CNS circuit are constructed through a recognition program based on repellent signaling.
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