Primary Cilia Signaling Shapes the Development of Interneuronal Connectivity.

Primary Cilia Signaling Shapes the Development of Interneuronal Connectivity.
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原发性纤毛信号传导塑造了神经元连通性的发展。

DOI:
10.1016/j.devcel.2017.07.010
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发表时间:
2017-08-07
期刊:
影响因子:
11.8
通讯作者:
Anton ES
Anton ES
中科院分区:
生物学1区
文献类型:
--
作者:
Guo J;Otis JM;Higginbotham H;Monckton C;Cheng J;Asokan A;Mykytyn K;Caspary T;Stuber GD;Anton ES

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GABA能抑制性中间神经元的适当生长和突触整合对于脑中的功能性神经回路是必不可少的。在这里,我们证明,中断初级纤毛功能后,选择性丧失纤毛GTAL-Arl 13 b在interneurons损害interneurons的形态和突触连接,导致改变兴奋/抑制活性(E/I)的平衡。纤毛突变体中间神经元的改变的形态和连接性和功能缺陷被拯救的纤毛GPCR信号的化学发生激活或选择性诱导Sstr 3,纤毛GPCR,在Arl 13 b缺陷纤毛。因此,我们的研究结果定义了一个特定的要求,初级纤毛介导的GPCR信号在神经元间的连接和抑制电路的形成。中间神经元的生长和连接是功能性神经回路形成的基础。Guo等人表明,初级纤毛信号通过Arl 13 b-GPCR途径促进神经元间的连接和抑制回路的形成。初级纤毛信号传导是一种非突触信号传导机制,环境信号可以通过该机制塑造和细化神经元间网络。
Appropriate growth and synaptic integration of GABAergic inhibitory interneurons are essential for functional neural circuits in the brain. Here, we demonstrate that disruption of primary cilia function following the selective loss of ciliary GTPase Arl13b in interneurons impairs interneuronal morphology and synaptic connectivity, leading to altered excitatory/inhibitory activity (E/I) balance. The altered morphology and connectivity of cilia mutant interneurons and the functional deficits are rescued by either chemogenetic activation of ciliary GPCR signaling or the selective induction of Sstr3, a ciliary-GPCR, in Arl13b deficient cilia. Our results thus define a specific requirement for primary cilia-mediated GPCR signaling in interneuronal connectivity and inhibitory circuit formation. Growth and connectivity of interneurons are fundamental to the formation of functional neural circuitry. Guo et al. show that primary cilia signaling, via Arl13b-GPCR pathway, promotes interneuronal connectivity and inhibitory circuit formation. Primary cilia signaling is a non-synaptic signaling mechanism through which environmental signals can shape and refine interneuronal networks.
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