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对 耳蜗核(CN)，以及耳聋后这些输入的改变如何可能导致重新组织 导致幻音或耳鸣的双峰相互作用。 这一资助期的一个重要发现是，刺激三叉神经细胞可以显著地 抑制背侧CN(DCN)单位的声驱动反应。这表明躯体感觉- 听觉整合可能涉及对内部产生的声音的抑制，如自我 发声或呼吸。研究这种双峰集成背后的机制将使我们能够 了解DCN在改进对外部新刺激的检测方面的作用。目标1将描述 三叉神经脊束核(SP5)和外侧网状结构(RF)向CN的投射。电学上 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中双峰整合的潜在机制。这个 被引用来解释长期整合的假设包括长期抑郁/增强， 短暂的钾通道激活，或GABAB受体激活。这些假设将使用以下方法进行测试 多通道记录探头，使我们能够从大量的单元同时进行记录。这个 重点将放在DCN单位对三叉神经刺激的反应中的临时放电模式的变化。 目标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单位的临时放电模式的改变可能反映了固有的改变 膜特性或耳蜗病后三叉神经传入神经数目的增加。这个 噪声损伤后三叉神经支配可能增加的假说将使用 囊泡谷氨酸和GAP-43/突触素/突触素1免疫细胞化学结合束 追踪。神经元之间同步性增强可能与耳鸣和规律性改变有关 与三叉神经刺激同步可能与躯体耳鸣有关。因此，检查中断 耳蜗损伤后双峰整合的研究将使我们能够阐明潜在的机制 耳鸣，从而为指导临床干预提供见解。

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.