Sex-Related Differential Whole-Brain Input Atlas of Locus Coeruleus Noradrenaline Neurons.

Sex-Related Differential Whole-Brain Input Atlas of Locus Coeruleus Noradrenaline Neurons.
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蓝斑去甲肾上腺素神经元的性别相关差异全脑输入图谱

DOI:
10.3389/fncir.2020.00053
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发表时间:
2020
影响因子:
3.5
通讯作者:
Zhang YH
Zhang YH
中科院分区:
医学3区
文献类型:
--
作者:
Sun P;Wang J;Zhang M;Duan X;Wei Y;Xu F;Ma Y;Zhang YH

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大脑作为我们身体中最重要的器官,在决定性别相关的差异特征方面起着至关重要的作用;然而,潜在的神经回路基础仍然不清楚。在这里,我们使用细胞类型特异性狂犬病毒介导的单突触追踪系统,以产生一个性别差异相关的蓝斑去甲肾上腺素(LC-NE)神经元的全脑输入图谱。我们开发了自定义管道,用于在两种性别中对输入源进行全脑比较,并将全脑数据集注册到艾伦小鼠脑参考图谱中。在257个不同的解剖区域中,我们证明了雄性和雌性小鼠不同水平的LC-NE神经元输入的不同比例。两种性别的蓝斑去甲肾上腺素神经元在输入模式上表现出普遍的相似性,但在主要脑区和不同的子区的定量输入比例上存在差异。例如,男性LC-NE神经元的输入主要发现在大脑,间脑,小脑,而女性LC-NE神经元的输入发现在中脑和后脑。我们进一步发现,嵌套在子区域内的特定子集的细胞核的输入电路的整体性别相关的差异。此外,在输入比例> 0.1%的123个解剖区域中,我们还发现11个亚区域的总输入在雌雄小鼠之间存在显著的统计学差异,其中7个亚区域在同侧半球也存在这种差异。我们的研究不仅提供了一个结构基础,以促进我们在电路水平上的性别差异的理解,但也提供了线索,为未来的性分化相关的LC-NE神经元的功能研究。
As the most important organ in our bodies, the brain plays a critical role in deciding sex-related differential features; however, the underlying neural circuitry basis remains unclear. Here, we used a cell-type-specific rabies virus-mediated monosynaptic tracing system to generate a sex differences-related whole-brain input atlas of locus coeruleus noradrenaline (LC-NE) neurons. We developed custom pipelines for brain-wide comparisons of input sources in both sexes with the registration of the whole-brain data set to the Allen Mouse Brain Reference Atlas. Among 257 distinct anatomical regions, we demonstrated the differential proportions of inputs to LC-NE neurons in male and female mice at different levels. Locus coeruleus noradrenaline neurons of two sexes showed general similarity in the input patterns, but with differentiated input proportions quantitatively from major brain regions and diverse sub-regions. For instance, inputs to male LC-NE neurons were found mainly in the cerebrum, interbrain, and cerebellum, whereas inputs to female LC-NE neurons were found in the midbrain and hindbrain. We further found that specific subsets of nuclei nested within sub-regions contributed to overall sex-related differences in the input circuitry. Furthermore, among the totaled 123 anatomical regions with proportion of inputs >0.1%, we also identified 11 sub-regions with significant statistical differences of total inputs between male and female mice, and seven of them also showed such differences in ipsilateral hemispheres. Our study not only provides a structural basis to facilitate our understanding of sex differences at a circuitry level but also provides clues for future sexually differentiated functional studies related to LC-NE neurons.
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