Brain asymmetry is encoded at the level of axon terminal morphology.

Brain asymmetry is encoded at the level of axon terminal morphology.
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大脑不对称性在轴突末端形态的水平上编码。

DOI:
10.1186/1749-8104-3-9
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发表时间:
2008-03-31
期刊:
影响因子:
3.6
通讯作者:
Wilson SW
Wilson SW
中科院分区:
生物学3区
文献类型:
--
作者:
Bianco IH;Carl M;Russell C;Clarke JD;Wilson SW

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功能偏侧化是中枢神经系统(CNS)的一个保守特征。然而,神经回路内潜在的左右不对称性及其发育机制却鲜有描述。 在这项研究中,我们利用局部电穿孔技术来检测偏侧缰核单个神经元的形态和连接性。大脑两侧的缰核投射神经元具有一种定型的单极形态,并在其靶标脚间核中形成显著的螺旋状终末树突分支,这种形态与迄今所描述的任何其他类型的神经元都不同。存在两种截然不同的轴突树突分支亚型,它们在分支形态以及在靶标核内的定位上都有所不同。关键的是,左右两侧的神经元都会形成这两种树突分支形态,但频率差异很大。我们表明,细胞类型组成的这些差异解释了左右缰核所表现出的总体连接不对称性。对单个突触后神经元的形态和投射的分析表明,靶标核有能力整合左右输入或独立处理它们,可能在不同的下游通路中传递来自左右缰核的信息,从而保留左右编码。此外,我们发现来自单侧左侧松果旁核的信号对于左右轴突形成具有适当形态和靶向的树突分支是必需的。然而,在松果旁核切除后,左右缰核神经元仍继续形成具有明显偏侧化形态的树突分支。 通过将不对称神经回路的分析推进到单细胞水平,我们解析了回路微观结构中的左右差异,并表明在单个投射神经元轴突的形态和连接性水平上可以识别偏侧化。至关重要的是,大脑两侧都指定了相同的回路组件,但不同神经元亚型比例的差异导致了偏侧化的神经结构和总体连接不对称性。尽管来自松果旁核的信号对于正常偏侧化的发育至关重要,但在发育过程中显然还有其他因素作用于这个高度保守的回路,赋予神经元左右特性。
Functional lateralization is a conserved feature of the central nervous system (CNS). However, underlying left-right asymmetries within neural circuitry and the mechanisms by which they develop are poorly described. In this study, we use focal electroporation to examine the morphology and connectivity of individual neurons of the lateralized habenular nuclei. Habenular projection neurons on both sides of the brain share a stereotypical unipolar morphology and elaborate remarkable spiraling terminal arbors in their target interpeduncular nucleus, a morphology unlike that of any other class of neuron described to date. There are two quite distinct sub-types of axon arbor that differ both in branching morphology and in their localization within the target nucleus. Critically, both arbor morphologies are elaborated by both left and right-sided neurons, but at greatly differing frequencies. We show that these differences in cell type composition account for the gross connectional asymmetry displayed by the left and right habenulae. Analysis of the morphology and projections of individual post-synaptic neurons suggests that the target nucleus has the capacity to either integrate left and right inputs or to handle them independently, potentially relaying information from the left and right habenulae within distinct downstream pathways, thus preserving left-right coding. Furthermore, we find that signaling from the unilateral, left-sided parapineal nucleus is necessary for both left and right axons to develop arbors with appropriate morphology and targeting. However, following parapineal ablation, left and right habenular neurons continue to elaborate arbors with distinct, lateralized morphologies. By taking the analysis of asymmetric neural circuitry to the level of single cells, we have resolved left-right differences in circuit microarchitecture and show that lateralization can be recognized at the level of the morphology and connectivity of single projection neuron axons. Crucially, the same circuitry components are specified on both sides of the brain, but differences in the ratios of different neuronal sub-types results in a lateralized neural architecture and gross connectional asymmetry. Although signaling from the parapineal is essential for the development of normal lateralization, additional factors clearly act during development to confer left-right identity upon neurons in this highly conserved circuit.
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