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经验依赖的树突棘在小鼠视觉皮层中的发育。

Experience-Dependent Development of Dendritic Arbors in Mouse Visual Cortex.

机构信息

Department of Biology.

Volen Center for Complex Systems.

出版信息

J Neurosci. 2020 Aug 19;40(34):6536-6556. doi: 10.1523/JNEUROSCI.2910-19.2020. Epub 2020 Jul 15.

Abstract

The dendritic arbor of neurons constrains the pool of available synaptic partners and influences the electrical integration of synaptic currents. Despite these critical functions, our knowledge of the dendritic structure of cortical neurons during early postnatal development and how these dendritic structures are modified by visual experience is incomplete. Here, we present a large-scale dataset of 849 3D reconstructions of the basal arbor of pyramidal neurons collected across early postnatal development in visual cortex of mice of either sex. We found that the basal arbor grew substantially between postnatal day 7 (P7) and P30, undergoing a 45% increase in total length. However, the gross number of primary neurites and dendritic segments was largely determined by P7. Growth from P7 to P30 occurred primarily through extension of dendritic segments. Surprisingly, comparisons of dark-reared and typically reared mice revealed that a net gain of only 15% arbor length could be attributed to visual experience; most growth was independent of experience. To examine molecular contributions, we characterized the role of the activity-regulated small GTPase Rem2 in both arbor development and the maintenance of established basal arbors. We showed that Rem2 is an experience-dependent negative regulator of dendritic segment number during the visual critical period. Acute deletion of Rem2 reduced directionality of dendritic arbors. The data presented here establish a highly detailed, quantitative analysis of basal arbor development that we believe has high utility both in understanding circuit development as well as providing a framework for computationalists wishing to generate anatomically accurate neuronal models. Dendrites are the sites of the synaptic connections among neurons. Despite their importance for neural circuit function, only a little is known about the postnatal development of dendritic arbors of cortical pyramidal neurons and the influence of experience. Here we show that the number of primary basal dendritic arbors is already established before eye opening, and that these arbors primarily grow through lengthening of dendritic segments and not through addition of dendritic segments. Surprisingly, visual experience has a modest net impact on overall arbor length (15%). Experiments in KO animals revealed that the gene Rem2 is positive regulator of dendritic length and a negative regulator of dendritic segments.

摘要

神经元的树突分支限制了可用的突触伙伴池,并影响突触电流的电整合。尽管这些功能至关重要,但我们对皮质神经元出生后早期发育过程中的树突结构以及这些树突结构如何被视觉经验所改变的了解并不完整。在这里,我们呈现了一个大规模的数据集,其中包含了 849 个来自雄性和雌性小鼠视觉皮层出生后早期发育过程中收集的 3D 重建的基底树突的图像。我们发现,基底树突在出生后第 7 天(P7)到 P30 之间有显著的生长,总长度增加了 45%。然而,初级神经突和树突段的数量主要由 P7 决定。从 P7 到 P30 的生长主要通过树突段的延伸来实现。令人惊讶的是,对暗养和常规饲养小鼠的比较表明,只有 15%的树突长度的净增长可以归因于视觉经验;大多数生长都是独立于经验的。为了研究分子贡献,我们描述了活性调节的小 GTPase Rem2 在树突发育和已建立的基底树突的维持中的作用。我们表明,Rem2 是视觉关键期内树突段数量的经验依赖性负调节因子。Rem2 的急性缺失降低了树突分支的方向性。这里呈现的数据建立了一个高度详细的基底树突发育的定量分析,我们认为它在理解电路发育以及为希望生成解剖学上准确的神经元模型的计算人员提供框架方面都具有很高的实用性。树突是神经元之间突触连接的部位。尽管它们对神经回路功能很重要,但我们对皮质锥体神经元的树突分支的出生后发育以及经验的影响知之甚少。在这里,我们表明,初级基底树突的数量在眼睛睁开之前就已经确定,并且这些树突主要通过树突段的伸长而不是通过树突段的添加来生长。令人惊讶的是,视觉经验对整体树突长度只有适度的净影响(15%)。KO 动物的实验表明,基因 Rem2 是树突长度的正调节因子,也是树突段的负调节因子。

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