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高尔基极性转移通过介导 NMDA 受体信号转导指导新生儿皮层树突细化。

Golgi polarity shift instructs dendritic refinement in the neonatal cortex by mediating NMDA receptor signaling.

机构信息

Laboratory of Mammalian Neural Circuits, National Institute of Genetics (NIG), Mishima, Shizuoka 411-8540, Japan; Graduate Institute for Advanced Studies, SOKENDAI, Mishima, Shizuoka 411-8540, Japan.

出版信息

Cell Rep. 2023 Aug 29;42(8):112843. doi: 10.1016/j.celrep.2023.112843. Epub 2023 Jul 28.

Abstract

Dendritic refinement is a critical component of activity-dependent neuronal circuit maturation, through which individual neurons establish specific connectivity with their target axons. Here, we demonstrate that the developmental shift of Golgi polarity is a key process in dendritic refinement. During neonatal development, the Golgi apparatus in layer 4 spiny stellate (SS) neurons in the mouse barrel cortex lose their original apical positioning and acquire laterally polarized distributions. This lateral Golgi polarity, which is oriented toward the barrel center, peaks on postnatal days 5-7 (P5-P7) and disappears by P15, which aligns with the developmental time course of SS neuron dendritic refinement. Genetic ablation of N-methyl-D-aspartate (NMDA) receptors, key players in dendritic refinement, disturbs the lateral Golgi polarity. Golgi polarity manipulation disrupts the asymmetric dendritic projection pattern and the primary-whisker-specific response of SS neurons. Our results elucidate activity-dependent Golgi dynamics and their critical role in developmental neuronal circuit refinement.

摘要

树突细化是活性依赖的神经元回路成熟的关键组成部分,通过该过程,单个神经元与其靶轴突建立特定的连接。在这里,我们证明了高尔基体极性的发育转变是树突细化的关键过程。在新生发育过程中,小鼠桶状皮层第 4 层棘状星状(SS)神经元中的高尔基体装置失去了原始的顶端定位,并获得了侧向极化分布。这种朝向桶状中心的侧向高尔基体极性在出生后第 5-7 天(P5-P7)达到峰值,并在 P15 时消失,与 SS 神经元树突细化的发育时间进程一致。N-甲基-D-天冬氨酸(NMDA)受体的基因缺失,树突细化的关键参与者,扰乱了侧向高尔基体极性。高尔基体极性的操纵破坏了 SS 神经元的不对称树突投射模式和初级触须特异性反应。我们的结果阐明了活性依赖的高尔基体动力学及其在发育中的神经元回路细化中的关键作用。

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