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）：本研究项目的长期目标是阐明耳蜗核（CN）的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，从而导致幻觉声音或耳鸣的感知。从这个资助期的一个重要发现是，刺激三叉神经可以显著抑制声驱动的反应在背CN （DCN）单位。这表明，体感-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在改善对外部新刺激的检测方面的作用。目的1将描述从脊髓三叉神经核（Sp5）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DCN内听觉处理的贡献。目的2将确定DCN中双峰整合的机制。用来解释长期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针进行测试，使我们能够同时从大量单元进行记录。重点将是在响应三叉神经刺激的DCN单元的颞放电模式的变化。目的3将探讨我们最近的观察结果，即耳蜗损伤后DCN单元对三叉神经刺激更敏感：耳蜗损伤后DCN单元颞叶放电模式的变化可能反映了内质膜特性的改变或三叉神经输入数量的增加。我们将利用囊泡谷氨酸和GAP-43/synaptophysin/synapsin1免疫细胞化学结合通道示踪来研究噪声损伤后三叉神经的神经分布可能增加的假设。神经元间的同步性增加可能与耳鸣有关，三叉神经刺激的规律性和同步性的变化可能与躯体耳鸣有关。因此，检查耳蜗损伤后双峰整合的破坏将使我们能够阐明耳鸣的机制，从而为指导临床干预提供见解。