A key subset of receptors involved in spinal-mediated biological rhythms

参与脊髓介导的生物节律的受体的关键子集

• 批准号: RGPIN-2016-05846
• 负责人: Guertin, Pierre
• 金额: $ 2.26万
• 依托单位: Université Laval
• 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=683731
• 关键词: key; subset; receptors; involved; spinal

*Biological rhythms underlie most vital functions in virtually all living organisms from plants to mammals. In vertebrate species, the circadian rhythm is probably, as of now, one the best characterized rhythmic functions. It involves the release of several chemicals such as gamma-aminobutyric acid, melatonin and serotonin (5-HT) that act specifically upon some of their receptor subtypes in the brain. With NSERC funding, my group has found evidence suggesting the existence of a partially comparable mechanism involved in the control of another rhythmic function that is locomotion. A few years ago, using pharmacological, surgical, and genetic approaches, we found indeed a key role as a trigger' of locomotor activity for a specific subtype (1A) of 5-HT receptors located in the lumbar spinal cord. We recently expanded those observations by providing additional evidence that other spinal-mediated rhythmic functions such as micturition, defecation and ejaculation critically depend also upon activation of 5-HT1A receptors. However, several important questions remain to be elucidated prior to understand fully the complex role of 5-HT in biological rhythms, specifically in the spinal cord. For instance, what role descending signals from brain or sensory signals from peripheral nerves play in spinal 5-HT1A receptor-mediated rhythms? What contributions other subtypes or families of receptors and their intracellular signals have in such spinal functions? These kinds of questions, addressed in my research program, are particularly exciting given their potential to unravel the details of this new role of 5-HT as a trigger' of neural oscillatory activities, in parallel to its more widely known role as a modulator' of neural functions. As such it will shed a new light on the complexity of 5-HT actions in vertebrate species generally inhibitory in the brain and apparently also excitatory in the spinal cord. It is not unreasonable to think that findings from the proposed research will eventually help other researchers revisiting the physiology of brain-mediated rhythmic functions such as sleeping, alertness, or hormonal release. I strongly believe that this research program will provide a rich and fruitful training experience for several graduate and undergraduate students here at Laval University.

* 生物节律是从植物到哺乳动物的几乎所有生物体的大多数重要功能的基础。在脊椎动物物种中，昼夜节律可能是迄今为止最具特征的节律功能之一。它涉及释放几种化学物质，如γ-氨基丁酸，褪黑激素和5-羟色胺（5-HT），这些化学物质专门作用于大脑中的一些受体亚型。在NSERC的资助下，我的团队发现了证据，表明存在一种部分可比较的机制，涉及另一种节律功能，即运动。几年前，通过药理学、外科手术和遗传学方法，我们确实发现了位于腰髓中的5-HT受体的一种特定亚型（1A）作为自发活动的触发器的关键作用。我们最近通过提供其他证据扩展了这些观察结果，这些证据表明其他脊髓介导的节律功能，如排尿，排便和射精也严重依赖于5-HT 1A受体的激活。然而，在完全理解5-HT在生物节律中的复杂作用之前，仍有几个重要的问题有待阐明，特别是在脊髓中。例如，来自大脑的下行信号或来自外周神经的感觉信号在脊髓5-HT1A受体介导的节律中起什么作用？其他受体亚型或家族及其细胞内信号在脊髓功能中有何作用？在我的研究项目中提出的这类问题特别令人兴奋，因为它们有可能揭示5-HT作为神经振荡活动触发器的新作用的细节，同时它作为神经功能调制器的作用更为广泛。因此，它将揭示一个新的光的复杂性5-羟色胺行动在脊椎动物物种通常抑制在大脑中，显然也兴奋在脊髓。认为这项研究的结果最终将帮助其他研究人员重新审视大脑介导的节律功能（如睡眠、警觉或激素释放）的生理学，这并不是不合理的。我坚信，这个研究项目将为拉瓦尔大学的研究生和本科生提供丰富而富有成效的培训经验。