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

从植物到哺乳动物，几乎所有生物的最重要功能都是由生物节律决定的。到目前为止，在脊椎动物物种中，昼夜节律可能是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、褪黑激素和血清素（5-HT），这些化学物质专门作用于大脑中的某些受体亚型。在NSERC的资助下，我的团队发现了证据，表明存在一种部分类似的机制，涉及控制另一种节律功能，即运动。几年前，通过药理学、外科手术和遗传学方法，我们发现位于腰椎的5-羟色胺受体的一种特定亚型（1A）确实具有触发运动活动的关键作用。我们最近扩大了这些观察结果，提供了额外的证据，证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-HT1A受体的激活。然而，在充分理解5-羟色胺在生物节律中的复杂作用，特别是在脊髓中的作用之前，仍有几个重要的问题有待阐明。例如，来自大脑的下行信号或来自周围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这些脊髓功能中有什么贡献？这类问题在我的研究计划中得到了解决，它们特别令人兴奋，因为它们有可能揭示5-羟色胺作为神经振荡活动的触发器的新作用的细节，与它作为神经功能调节剂的更广为人知的作用平行。因此，它将揭示脊椎动物物种中5-羟色胺作用的复杂性，通常在大脑中是抑制性的，在脊髓中显然也有兴奋性的。这项研究的发现最终将帮助其他研究人员重新审视大脑调节的节律功能（如睡眠、警觉性或激素释放）的生理学，这种想法并非没有道理。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。

*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.