选择性神经毒素 DSP-4 损害大鼠蓝斑至下丘的去甲肾上腺素能投射。

The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats.

机构信息

Institute for Neuroscience of Castilla y Leon, University of Salamanca Salamanca, Spain.

出版信息

Front Neural Circuits. 2012 Jun 28;6:41. doi: 10.3389/fncir.2012.00041. eCollection 2012.

Abstract

The inferior colliculus (IC) and the locus coeruleus (LC) are two midbrain nuclei that integrate multimodal information and play a major role in novelty detection to elicit an orienting response. Despite the reciprocal connections between these two structures, the projection pattern and target areas of the LC within the subdivisions of the rat IC are still unknown. Here, we used tract-tracing approaches combined with immunohistochemistry, densitometry, and confocal microscopy (CM) analysis to describe a projection from the LC to the IC. Biotinylated dextran amine (BDA) injections into the LC showed that the LC-IC projection is mainly ipsilateral (90%) and reaches, to a major extent, the dorsal and lateral part of the IC and the intercollicular commissure. Additionally, some LC fibers extend into the central nucleus of the IC. The neurochemical nature of this projection is noradrenergic, given that tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DBH) colocalize with the BDA-labeled fibers from the LC. To determine the total field of the LC innervations in the IC, we destroyed the LC neurons and fibers using a highly selective neurotoxin, DSP-4, and then studied the distribution and density of TH- and DBH-immunolabeled axons in the IC. In the DSP-4 treated animals, the number of axonal fibers immunolabeled for TH and DBH were deeply decreased throughout the entire rostrocaudal extent of the IC and its subdivisions compared to controls. Our densitometry results showed that the IC receives up to 97% of its noradrenergic innervations from the LC neurons and only 3% from non-coeruleus neurons. Our results also indicate that TH immunoreactivity in the IC was less impaired than the immunoreactivity for DBH after DSP-4 administration. This is consistent with the existence of an important dopaminergic projection from the substantia nigra to the IC. In conclusion, our study demonstrates and quantifies the noradrenergic projection from the LC to the IC and its subdivisions. The re-examination of the TH and DBH immunoreactivity after DSP-4 treatment provides insights into the source, extent, and topographic distribution of the LC efferent network in the IC, and hence, contributes to our understanding of the role of the noradrenaline (NA) system in auditory processing.

摘要

下丘(IC)和蓝斑核(LC)是两个中脑核团,它们整合多模态信息,在探测新奇性以引起定向反应方面发挥主要作用。尽管这两个结构之间存在相互联系,但 LC 在大鼠 IC 各亚区中的投射模式和靶区仍然未知。在这里,我们使用示踪方法结合免疫组织化学、密度测定和共聚焦显微镜(CM)分析来描述 LC 到 IC 的投射。将生物素化葡聚糖胺(BDA)注入 LC 后发现,LC-IC 投射主要是同侧(90%),并在很大程度上到达 IC 的背侧和外侧部分以及脑桥间连合。此外,一些 LC 纤维延伸到 IC 的中央核。该投射的神经化学性质为去甲肾上腺素能,因为酪氨酸羟化酶(TH)和多巴胺β羟化酶(DBH)与来自 LC 的 BDA 标记纤维共定位。为了确定 LC 在 IC 中的神经支配的总范围,我们使用高度选择性神经毒素 DSP-4 破坏 LC 神经元和纤维,然后研究了 IC 中 TH 和 DBH 免疫标记轴突的分布和密度。在 DSP-4 处理的动物中,与对照组相比,TH 和 DBH 免疫标记的轴突纤维在整个 IC 的前后轴上以及其各亚区的数量都明显减少。我们的密度测定结果表明,IC 接收来自 LC 神经元的去甲肾上腺素能支配高达 97%,而仅来自非蓝斑神经元的支配为 3%。我们的结果还表明,在 DSP-4 给药后,IC 中的 TH 免疫反应性比 DBH 免疫反应性受损更小。这与来自黑质的重要多巴胺能投射到 IC 是一致的。总之,我们的研究证明并量化了 LC 到 IC 及其各亚区的去甲肾上腺素能投射。在 DSP-4 处理后重新检查 TH 和 DBH 免疫反应性,为我们理解 LC 传出网络在 IC 中的来源、范围和拓扑分布提供了新的视角,从而有助于我们理解去甲肾上腺素(NA)系统在听觉处理中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc10/3385004/0880c8b1b5f3/fncir-06-00041-g0001.jpg

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