Function of trigeminal pathways to the cochlear nucleus

通向耳蜗核的三叉神经通路的功能

• 批准号: 7194660
• 负责人: SUSAN E SHORE
• 金额: $ 31.84万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7194660
• 关键词: Acoustic Stimulation; Acoustics; Animals; Area; Auditory; Chemosensitization; Clinical; Cochlear nucleus; Deafferentation procedure; Dependence; Detection; Disruption; Dorsal; Electric Stimulation; Fire - disasters; Funding; Fusiform Cell; Glutamates; Goals; Growth Associated Protein 43; Intervention; Label; Lateral; Lead; Learning; Long-Term Depression; Mediating; Membrane; N-Methyl-D-Aspartate Receptors; Neurons; Noise; Numbers; Outcome; Pathway interactions; Pattern; Perception; Physiological; Potassium Channel; Process; Property; Rate; Receptor Activation; Research; Research Personnel; Respiration; Reticular Formation; Role; Shapes; Site; Source; Stimulus; Structure of trigeminal ganglion; Structure of trigeminal nerve spinal tract nucleus; Synaptophysin; System; Testing; Time; Tinnitus; Training; Transcriptional Activation; Trigeminal System; Up-Regulation; cytochemistry; deafness; dorsal cochlear nucleus; experience; granule cell; improved; insight; nerve supply; novel; programs; receptor; research study; response; somatosensory; sound; time interval; vocalization

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.

描述（由申请人提供）：该研究计划的长期目标是阐明非原告输入对耳蜗核（CN）的正常作用，以及在耳聋后这些输入的变化如何导致双峰相互作用的重新组织，从而导致phantomsouns或Tinnnitus感知的双峰相互作用。从这个资金期间的一个重要发现是，刺激三叉神经元可以极大地抑制背CN（DCN）单位的声学驱动的反应。这表明，体感觉听觉整合可能与内部生成的声音（例如自发声或呼吸）有关。研究这种双峰整合的基础机制将使我们能够理解DCN在改善外部，新型刺激的检测中的作用。 AIM 1将描述从脊柱三叉神经核（SP5）和侧面网状形成（RF）到CN的投影。电力刺激这些区域将使我们能够进一步了解它们对DCN内听觉处理的贡献。 AIM 2将确定DCN中双峰整合的基础机制。引用的假设解释了持久的整合，包括长期抑郁/增强，瞬态钾通道激活或GABAB受体激活。这些假设将使用多通道记录探针进行测试，从而使我们能够从大量单元中同时记录。重点将放在响应三叉神经刺激的DCN单元的时间射击模式上。 AIM 3将探讨我们最近的观察结果，即DCN单位对人工耳蜗损害后对三叉神经刺激的敏感性更高：DCN单元的时间发射模式的变化可能反映了内在的膜特性的改变，或者在耳蜗损害后的三叉戟输入数量增加。在噪声损伤后可能会增加三叉神经支配的假说将使用囊泡谷氨酸和GAP-43/Synaptophysin/Synapsin1免疫细胞化学结合结合道跟踪。神经元之间的同步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变化可能是细胞鸣的相关性。因此，检查人工耳蜗损害后双峰整合的破坏将使我们能够阐明耳鸣的基础机制，从而提供见解以指导临床干预。