Role of the trigeminal ganglion in sensory processing

三叉神经节在感觉处理中的作用

• 批准号: RGPIN-2017-03742
• 负责人: Cairns, Brian
• 金额: $ 1.82万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=681117
• 关键词: Role; trigeminal; ganglion; sensory; processing

The sensory ganglia are often considered a passive conduit of action potentials that arise in the periphery and travel to the central nervous system. Until relatively recently, very little attention has been paid to the possibility that the ganglion could potentially modify sensory transmission. However, several groups have reported that intraganglionic injection of small interfering RNA against targets such as the gamma-aminobutyric acid (GABA) A receptor, or viral vectors containing genes for various enzymes have effects on sensory transmission. Trigeminal ganglia are comprised of ganglion neurons and two types of glial cells, satellite glial cells (SGCs) and Schwann cells. The soma of the trigeminal ganglion neuron is surrounded by SGCs, with a gap of about 20 nm between the neuronal and SGC cell membranes. It is thought that SGCs modulate the activity of ganglion neurons by releasing neuromodulatory substances into this gap. Trigeminal ganglion neurons express receptors for many neurotransmitters, but the functional effect of activation of these receptors on sensory transmission is largely unknown. We investigated whether activated SGCs release the excitatory amino acid glutamate and if this would depolarize trigeminal ganglion neurons to cause ectopic action potential generation towards the brain (orthodromic) and the periphery (antidromic). We found that artificially elevated glutamate levels in the trigeminal ganglion did cause trigeminal ganglion neurons to fire action potentials and that this was associated with mechanical sensitization of trigeminal afferent fibers that innervate facial tissues. Action potential discharge evoked by injection of glutamate into the trigeminal ganglion was mediated by N-Methyl-D-Aspartate (NMDA) receptor activation and could be enhanced by blocking excitatory amino acid transporters (EAATs) that were found on both neurons and SGCs. These findings suggest that alteration in glutamate concentration in the ganglion can alter sensory thresholds and offer the possibility that sensory information may be modulated at this level by other neurotransmitters. This application proposes to investigate the effect neurotransmitters on the activity of trigeminal ganglion neurons and satellite glial cells, and to determine how these neuroactive substances alter sensory transmission through the ganglia and whether there are sex-related differences appear to influence peripheral processing of sensory information. An overarching goal of this research is to determine whether significant neural processing of sensory information occurs at the level of the trigeminal sensory ganglion. The goal is to understand how ganglion neuron satellite glial cell communication modifies the transmission of sensory information through the ganglion. This work may identify peripheral mechanisms that could be targeted to modify altered sensory input.

感觉神经节通常被认为是动作电位的被动通道，这些动作电位产生于外周神经系统，并传递到中枢神经系统。直到最近，很少有人注意到神经节可能潜在地改变感觉传递的可能性。然而，一些研究小组已经报道，在神经节内注射小干扰RNA来对抗目标，如γ -氨基丁酸（GABA） A受体，或含有各种酶基因的病毒载体，对感觉传递有影响。三叉神经节由神经节神经元和卫星神经胶质细胞（sgc）和雪旺细胞两种胶质细胞组成。三叉神经节神经元的胞体被SGC包围，神经元和SGC细胞膜之间约有20 nm的间隙。据认为，SGCs通过释放神经调节物质进入这个间隙来调节神经节神经元的活动。三叉神经节神经元表达许多神经递质的受体，但这些受体的激活对感觉传递的功能影响在很大程度上是未知的。我们研究了激活的SGCs是否释放兴奋性氨基酸谷氨酸，以及这是否会使三叉神经节神经元去极化，从而导致向大脑（正侧）和外周（反侧）产生异位动作电位。我们发现，人工升高三叉神经节中的谷氨酸水平确实导致三叉神经节神经元激发动作电位，这与支配面部组织的三叉神经传入纤维的机械致敏有关。三叉神经节注射谷氨酸引起的动作电位放电是由n -甲基- d -天冬氨酸（NMDA）受体激活介导的，并可通过阻断神经元和SGCs上的兴奋性氨基酸转运蛋白（EAATs）而增强。这些发现表明神经节中谷氨酸浓度的改变可以改变感觉阈值，并提供了感觉信息可能在这一水平上被其他神经递质调节的可能性。本申请拟研究神经递质对三叉神经节神经元和卫星胶质细胞活性的影响，并确定这些神经活性物质如何改变神经节的感觉传递，以及是否存在性别相关差异影响感觉信息的外周加工。本研究的首要目标是确定三叉神经感觉神经节是否对感觉信息进行重要的神经处理。目的是了解神经节神经元卫星胶质细胞通讯如何改变通过神经节的感觉信息传递。这项工作可能会确定外围机制，可以有针对性地修改改变的感觉输入。