Function of trigeminal pathways to the cochlear nucleus

这项研究计划的长期目标是阐明非听觉输入的正常作用， 耳蜗核（CN），以及耳聋后这些输入的改变如何导致重组 导致幻听或耳鸣的感觉。 在这段资助期内的一个重要发现是，刺激三叉神经元可以显著地 抑制背侧CN（DCN）单位的声学驱动反应。这表明躯体感觉- 听觉整合可能涉及抑制内部产生的声音， 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。目标1将描述 从三叉神经脊束核（Sp 5）和外侧网状结构（RF）到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听觉处理的贡献， DCN。目标二将确定DCN中双峰整合的机制。的 用来解释持久整合的假设包括长期抑制/增强， 瞬时钾通道激活或GABAB受体激活。这些假设将被测试使用 多通道记录探头，使我们能够同时记录大量的单位。的 重点将放在三叉神经刺激后DCN单位的瞬时放电模式的变化上。 目的三将探讨我们最近观察到的DCN单位对三叉神经刺激变得更加敏感 耳蜗损伤后：DCN单位的时间放电模式的变化可能反映了耳蜗损伤后DCN单位的内在变化。 膜特性或耳蜗损伤后三叉神经输入数量的增加。的 假设噪声损伤后三叉神经支配可能增加，将使用 囊泡谷氨酸和GAP-43/synaptophysin/synapsin 1免疫细胞化学结合束 追踪神经元之间的同步性增加可能是耳鸣和规律性变化的相关性， 与三叉神经刺激同步可能与躯体耳鸣相关。因此，检查中断 耳蜗损伤后的双峰整合将使我们能够阐明潜在的机制 耳鸣，从而提供指导临床干预的见解。

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 two 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 hypotheseswill 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 three 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.