Tinnitus, unipolar brush cells, and cerebellar glutamatergic function in an animal model.

Tinnitus, unipolar brush cells, and cerebellar glutamatergic function in an animal model.
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DOI:
10.1371/journal.pone.0064726
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Brozoski TJ
Brozoski TJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bauer CA;Wisner KW;Baizer JS;Brozoski TJ

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单极刷状细胞(Unipolar brush cells,UBC)是位于耳蜗背核(dorsal cochlear nucleus,DCN)和小脑皮质颗粒细胞层的兴奋性中间神经元,在副绒球(paraflocculus,PFL)和绒球(flocculus,FL)中尤为明显。UBC接受突触能输入,并与颗粒细胞和其他UBC形成突触能突触。已经假设UBC包括可调谐前馈放大器的本地网络。在DCN中,它们也可能参与来自高级听觉中心的信号的反馈放大。最近,它已被证明,UBC,在前庭小脑和DCN的成年大鼠,表达doublecortin(DCX),以前被认为是新生和迁移神经元的标记。在动物模型中,DCN和最近的PFL都与声音暴露引起的耳鸣的感觉有关。这些研究支持了耳鸣出现在外周敏感性丧失后的工作假设,因为抑制性过程稳态下调,兴奋性过程上调。在这里,我们报告了两个连续的实验,研究耳鸣的DCN和小脑UBC的潜在作用的结果,和PFL中的神经递质传递的贡献。在实验1中,结果表明,成年大鼠与耳鸣的心理物理证据引起的一个单一的单边高水平的噪声暴露,有升高的DCX在DCN和腹侧PFL。在实验2中,它表明,微量的β-amatergic拮抗剂,直接提供给PFL,可逆地减少慢性建立耳鸣,而类似地应用β-amatergic激动剂诱导耳鸣样行为在非耳鸣控制。这些结果与UBC上调和小脑中增强的神经递质传递有助于耳鸣的病理生理学的假设一致。
Unipolar brush cells (UBCs) are excitatory interneurons found in the dorsal cochlear nucleus (DCN) and the granule cell layer of cerebellar cortex, being particularly evident in the paraflocculus (PFL) and flocculus (FL). UBCs receive glutamatergic inputs and make glutamatergic synapses with granule cells and other UBCs. It has been hypothesized that UBCs comprise local networks of tunable feed-forward amplifiers. In the DCN they might also participate in feed-back amplification of signals from higher auditory centers. Recently it has been shown that UBCs, in the vestibulocerebellum and DCN of adult rats, express doublecortin (DCX), previously considered a marker of newborn and migrating neurons. In an animal model, both the DCN, and more recently the PFL, have been implicated in contributing to the sensation of acoustic-exposure-induced tinnitus. These studies support the working hypothesis that tinnitus emerges after loss of peripheral sensitivity because inhibitory processes homeostatically down regulate, and excitatory processes up regulate. Here we report the results of two sequential experiments that examine the potential role of DCN and cerebellar UBCs in tinnitus, and the contribution of glutamatergic transmission in the PFL. In Experiment 1 it was shown that adult rats with psychophysical evidence of tinnitus induced by a single unilateral high-level noise exposure, had elevated DCX in the DCN and ventral PFL. In Experiment 2 it was shown that micro-quantities of glutamatergic antagonists, delivered directly to the PFL, reversibly reduced chronically established tinnitus, while similarly applied glutamatergic agonists induced tinnitus-like behavior in non-tinnitus controls. These results are consistent with the hypothesis that UBC up regulation and enhanced glutamatergic transmission in the cerebellum contribute to the pathophysiology of tinnitus.
DOI: 10.1007/s101620010030
发表时间: 2001-03-01
影响因子: 2.4
作者:
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发表时间: 2000-09-01
期刊: HEARING RESEARCH
影响因子: 2.8
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DOI: 10.1111/j.1460-9568.2004.03813.x
发表时间: 2005-01-01
影响因子: 3.4
作者:
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