Function of trigeminal pathways to the cochlear nucleus

描述（由申请人提供）：本研究计划的长期目标是阐明耳蜗核（CN）非听觉输入的正常作用，以及耳聋后这些输入的改变如何导致双峰相互作用的重组，从而导致幻音或耳鸣的感知。在此资助期间的一个重要发现是，刺激三叉神经元可以显著抑制背侧CN（DCN）单位的声学驱动反应。这表明，躯体感觉-听觉整合可能参与抑制内部产生的声音，如自我发声或呼吸。研究这种双峰整合的机制将使我们能够理解DCN在改善外部新刺激检测方面的作用。目的1描述三叉神经脊束核（Sp 5）和外侧网状结构（RF）向CN的投射。电刺激这些区域将使我们能够更多地了解它们对DCN内听觉处理的贡献。目标2将确定DCN中双峰整合的机制。用于解释持久整合的假说包括长期抑制/增强、瞬时钾通道激活或GABAB受体激活。这些假设将使用多通道记录探头进行测试，使我们能够同时记录大量的单位。重点将是在三叉神经刺激的DCN单位的时间放电模式的变化。目的3将探讨我们最近的观察，DCN单位变得更敏感的三叉神经刺激耳蜗损伤后：DCN单位的时间放电模式的变化可能反映了改变内在膜特性或增加的数量三叉神经输入耳蜗损伤后。噪声损伤后三叉神经支配可能增加的假设将使用囊泡谷氨酸和GAP-43/synaptophysin/synapsin 1免疫细胞化学结合束追踪进行研究。神经元之间的同步性增加可能是耳鸣的相关性，并且与三叉神经刺激的规律性和同步性的变化可能是躯体耳鸣的相关性。因此，研究耳蜗损伤后双峰整合的破坏将使我们能够阐明耳鸣的潜在机制，从而提供指导临床干预的见解。

DESCRIPTION (provided by applicant): The long term goal of this research program is to elucidate both the normal role of non-auditory inputs to the cochlear nucleus (CN), and how alterations of these inputs after deafness may lead to a re-organization of bimodal interactions that result in the perception of phantom sounds or tinnitus. A significant finding from this funding period is that stimulating trigeminal neurons can dramatically suppress acoustically driven responses in dorsal CN (DCN) units. This suggests that somatosensory- auditory integration may be involved in the suppression of internally-generated sounds such as self vocalization or respiration. Investigating the mechanisms underlying this bimodal integration will allow us to appreciate the role of the DCN in improving the detection of external, novel stimuli. Aim 1 will describe the projections from the spinal trigeminal nucleus (Sp5) and lateral reticular formation (RF) to the CN. Electrically stimulating these regions will enable us to learn more about their contributions to auditory processing within the DCN. Aim 2 will determine the mechanisms underlying bimodal integration in the DCN. The hypotheses invoked to explain the long lasting integration include long term depression/potentiation, transient potassium channel activation, or GABAB receptor activation. These hypotheses will be tested using multichannel recording probes, enabling us to record simultaneously from a large number of units. The focus will be on the changes in temporal firing patterns of DCN units in response to trigeminal stimulation. Aim 3 will explore our recent observation that DCN units become more sensitive to trigeminal stimulation after cochlear damage: Changes in the temporal firing patterns of DCN units may reflect altered intrinsic membrane properties or an increase in the number of trigeminal inputs following cochlear damage. The hypothesis that trigeminal innervation may increase following noise damage will be investigated using vesicular glutamate and GAP-43/synaptophysin/synapsin1 immuno cytochemistry combined with tract tracing. Increased synchrony between neurons may be a correlate of tinnitus and changes in regularity and synchrony with trigeminal stimulation may be a correlate of somatic tinnitus. Thus, examining the disruption of bimodal integration following cochlear damage will allow us to elucidate the mechanisms underlying tinnitus, and thus provide insights to guide clinical intervention.