Glutamatergic Projections to the Cochlear Nucleus are Redistributed in Tinnitus
Glutamatergic Projections to the Cochlear Nucleus are Redistributed in Tinnitus
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DOI：
10.1016/j.neuroscience.2018.09.008
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发表时间：
2018-11-01
期刊：
影响因子：
3.3
通讯作者：
Shore, Susan E.
中科院分区：
文献类型：
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作者：
Heeringa, Amarins N.;Wu, Calvin;Shore, Susan E.
耳鸣改变耳蜗核(CN)的听觉-躯体感觉可塑性。相应地，双峰听觉-体感刺激治疗可以减轻动物和人类的耳鸣(Marks等人，2018年)。因此，我们假设耳鸣与CN的躯体感觉神经支配改变有关。在这里，我们研究了囊泡性谷氨酸转运体1和2(VGLUT1和VGLUT2)在CN中的表达，揭示了谷氨酸能从耳蜗体感系统投射到脑干听觉中枢。豚鼠被单边暴露在窄带噪声中，并使用间隙预脉冲抑制声惊厥的方法对其进行耳鸣行为测试。在进行生理和行为测量后，对大脑切片进行VGLUT1或VGLUT2免疫组织化学染色。测定同侧和对侧CN各区域的Puncta密度。耳鸣与同侧颗粒细胞域(GCD)和前腹侧CN(AVCN)的VGLUT2点状密度上调有关。此外，由于对侧VGLUT1表达下调，VGLUT1在AVCN和背侧CN深层(DCN3)的表达存在耳鸣相关的耳间不对称性。这些与耳鸣相关的谷氨酸能失衡在双峰刺激治疗后被逆转。耳鸣相关的同侧VGLUT2阳性投射的上调可能源于对GCD和AVCN的躯体感觉投射。这种上调可能是CN耳鸣的神经生理学特征的基础。逆转同侧CN内增加的谷氨酸能神经支配可能是治疗耳鸣的关键机制。(C)2018年IBRO。爱思唯尔有限公司出版。保留所有权利。
Tinnitus alters auditory-somatosensory plasticity in the cochlear nucleus (CN). Correspondingly, bimodal auditory-somatosensory stimulation treatment attenuates tinnitus, both in animals and humans (Marks et al., 2018). Therefore, we hypothesized that tinnitus is associated with altered somatosensory innervation of the CN. Here, we studied the expression of vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) in the CN, which reveals glutamatergic projections from the cochlea as well as somatosensory systems to this brainstem auditory center. Guinea pigs were unilaterally exposed to narrowband noise and behaviorally tested for tinnitus using gap-prepulse inhibition of the acoustic startle. Following physiological and behavioral measures, brain sections were immunohistochemically stained for VGLUT1 or VGLUT2. Puncta density was determined for each region of the ipsilateral and contralateral CN. Tinnitus was associated with an ipsilateral upregulation of VGLUT2 puncta density in the granule cell domain (GCD) and anteroventral CN (AVCN). Furthermore, there was a tinnitus-associated interaural asymmetry for VGLUT1 expression in the AVCN and deep layer of the dorsal CN (DCN3), due to contralateral downregulation of VGLUT1 expression. These tinnitus-related glutamatergic imbalances were reversed upon bimodal stimulation treatment. Tinnitus-associated ipsilateral upregulation of VGLUT2-positive projections likely derives from somatosensory projections to the GCD and AVCN. This upregulation may underlie the neurophysiological hallmarks of tinnitus in the CN. Reversing the increased ipsilateral glutamatergic innervation in the CN is likely a key mechanism in treating tinnitus. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.