Neuronal subsets in the geniculate ganglion

膝状神经节的神经元亚群

• 批准号: 6516286
• 负责人: ALBERT I FARBMAN
• 金额: $ 27.67万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6516286
• 关键词: cell death; electrophysiology; ganglions; gene expression; glia; innervation; laboratory rat; mechanical stress; neurogenesis; neurogenetics; neuronal guidance; neurons; neurotrophic factors; nucleic acid amplification techniques; pain; peripheral nervous system; polymerase chain reaction; sectioning; taste; taste buds; thalamus; tissue /cell culture

Neurons in the geniculate ganglion provide sensory innervation to: 1) taste buds on the anterior region of the tongue, via the chorda tympani nerve; 2) taste buds on the incisive papilla and the soft palate, via the greater superficial petrosal nerve; and 3) the skin near the ear via a cutaneous nerve. Preliminary studies in our laboratory showed that three high affinity neurotrophin receptor tyrosine kinases (trkA, trkB and trkC) are found in neurons of the geniculate ganglion. The ligands for these receptors are a family of secreted neurotrophic factors: trkA binds Nerve Growth Factor, trkB binds Brain-Derived Neurotrophic Factor and Neurotrophin-4, and trk C binds Neurotrophin-3. In pilot studies on identified single neurons of the rat geniculate ganglion we have found that they can be divided into subsets according to the trk genes they express. Moreover, we have evidence suggesting that trk expression by rat geniculate ganglion neurons changes during development. This research will test two hypotheses: 1) The division of geniculate ganglion neurons into sub-populations based on differences in trk gene expression is related to one or more of the following: a) the projection of 3 main nerve branches from the ganglion, b) the taste and other modalities associated with neurons in the geniculate ganglion, or c) possible differences in central projections of the neurons. We shall use tracer molecules and electrophysiology to identify specific neurons, and subject these to RNA amplification and PCR methodology to look for functional correlates of the differences in trk expression. Hypothesis 2: The changes in trk gene expression in geniculate ganglion neurons reflect major developmental events, such as axon outgrowth, innervation of the peripheral target tissue, naturally occurring cell death, or innervation of the central target. We shall use in vitro and in vivo methods to relate changes in trk expression during development to other major developmental events.

膝状神经节中的神经元提供感觉神经支配至：1）舌前部区域上的味蕾，经由鼓索神经; 2）切乳头和软腭上的味蕾，经由岩浅大神经;以及3）耳附近的皮肤，经由皮神经。本实验室的初步研究表明，在膝状体神经节的神经元中发现了三种高亲和力的神经营养因子受体酪氨酸激酶（trkA，trkB和trkC）。这些受体的配体是分泌的神经营养因子家族：trkA结合神经生长因子，trkB结合脑源性神经营养因子和神经营养因子-4，trk C结合神经营养因子-3。在对大鼠膝状体神经节单个神经元的初步研究中，我们发现它们可以根据其表达的trk基因分为不同的亚群。此外，我们有证据表明大鼠膝状体神经节神经元的trk表达在发育过程中发生变化。本研究将检验两个假设：1）基于trk基因表达的差异将膝状体神经节神经元划分为亚群与以下一个或多个相关：a）来自神经节的3个主要神经分支的投射，B）与膝状体神经节中的神经元相关的味觉和其他模态，或c）神经元的中枢投射的可能差异。我们将使用示踪分子和电生理学来识别特定的神经元，并将这些进行RNA扩增和PCR方法来寻找trk表达差异的功能相关性。假设二：trk基因在膝状体神经节神经元中表达的变化反映了主要的发育事件，如轴突生长、外周靶组织的神经支配、自然发生的细胞死亡或中枢靶的神经支配。我们将使用体外和体内的方法，与其他主要的发展事件在发展过程中的trk表达的变化。