Structural organization and functional roles of electrical synapses formed by Cx36-containing gap junctions in neural systems

神经系统中含有 Cx36 的间隙连接形成的电突触的结构组织和功能作用

• 批准号: RGPIN-2020-05386
• 负责人: Nagy, James
• 金额: $ 2.62万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763318
• 关键词: Structural; organization; functional; roles; electrical

Intercellular communication channels composed of connexin proteins form gap junctions between neurons, creating electrical synapses that mediate direct electrical neurotransmission. My group and others have found electrical synapses formed by connexin36 (Cx36) in many regions of brain and spinal cord. One of our long-term objectives is to extend knowledge of the functional roles of these synapses in neuronal circuitry. Here, we aim to acquire understanding of the requirements for electrical synapses in a neuronal system that governs fundamentally important physiological processes related to sexual behaviour. We have documented an abundance of electrical synapses connecting motoneurons at lower levels of the spinal cord. These motoneurons are unique because, unlike other motoneurons, they are linked by gap junctions and they are sexually dimorphic, meaning that they along with their target muscles are well developed in males and less so in females. These motoneurons control the activity of muscles in the pelvic floor that govern sexual behavior. Intermingled among these motoneurons are those that mediate contraction of the external urethral and external anal sphincters and that also appear to be linked by gap junctions. As in rodents, gap junctions between these motoneurons were found in humans. During elicitation of the urethrogenital reflex, which mimics motoneuronal activity during sexual activity, the dimorphic motoneurons and their target muscles are highly synchronously active. Such synchronization is a hallmark property conferred by electrical synapses. However, electrical coupling between sexually dimorphic motoneurons has not been studied, and nothing is known about how this coupling between these motoneurons innervating their different target muscles might be organized. This dimorphic system provides an ideal model in which the key features that electrical synapses confer in a neuronal network can be related to physiological functions subserved by that network. We hypothesize that electrical coupling is an essential element of dimorphic motoneurons and those innervating sphincter muscles, and is required for coordinating synchronous motoneuronal and target muscle activity during sexual behavior. We will use anatomical and electrophysiological approaches in normal and transgenic mice lacking Cx36 to establish the extent to which these synapses contribute to physiological processes related to sexual activity.

由连接蛋白组成的细胞间通讯通道在神经元之间形成间隙连接，产生介导直接电神经传递的电突触。我的研究小组和其他研究人员已经在大脑和脊髓的许多区域发现了由连接蛋白36 （Cx36）形成的电突触。我们的长期目标之一是扩展这些突触在神经回路中的功能角色的知识。在这里，我们的目标是获得对神经系统中电突触的需求的理解，这些神经系统控制着与性行为相关的重要生理过程。我们已经记录了大量的电突触在脊髓的较低水平连接运动神经元。这些运动神经元的独特之处在于，与其他运动神经元不同，它们是通过间隙连接连接起来的，而且它们是两性二态的，这意味着它们与目标肌肉一起在男性中发育良好，而在女性中发育较差。这些运动神经元控制骨盆底肌肉的活动，从而支配性行为。混杂在这些运动神经元之间的是那些调节外尿道和外肛门括约肌收缩的神经元，它们似乎也通过间隙连接连接在一起。与啮齿类动物一样，在人类身上也发现了这些运动神经元之间的间隙连接。在尿道生殖反射的激发过程中，二态运动神经元和它们的目标肌肉高度同步活跃。这种同步是电突触所赋予的特征。然而，两性二态运动神经元之间的电偶联尚未被研究过，而且对于支配不同目标肌肉的运动神经元之间的电偶联是如何组织的也一无所知。这种二态系统提供了一个理想的模型，在这个模型中，电突触赋予神经元网络的关键特征可以与该网络所提供的生理功能相关。我们假设电耦合是二态运动神经元和支配括约肌的运动神经元的基本元素，并且是在性行为中协调同步运动神经元和目标肌肉活动所必需的。我们将在缺乏Cx36的正常和转基因小鼠中使用解剖学和电生理学方法来确定这些突触在多大程度上促进与性活动相关的生理过程。