权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Nitric oxide modulation of locomotor control networks in the spinal cord and brainstem of a model vertebrate

一氧化氮对模型脊椎动物脊髓和脑干运动控制网络的调节

基本信息

批准号：
BB/F015488/1
负责人：
Keith Sillar
金额：
$ 45.85万
依托单位：
University of St Andrews
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF015488%2F1
关键词：
Nitric oxide modulation locomotor control

项目摘要

Only 20 years ago it was discovered that free radical gas nitric oxide is an important biological signalling molecule which controls the diameter of blood vessels. Since then nitric oxide has been found to play a wide variety of important roles in other types of tissue including the brain where it regulates nerve cell development, as well as numerous brain functions like learning and memory. How nitric oxide is able to participate in regulating electrical activity in virtually every region of the brain is still a bit of a mystery. However, we know that certain nerve cells can make and release nitric oxide which then controls the ability of other nerve cells to communicate with each other. One of the reasons why it has been difficult to make progress in because the brain of adult animals, especially mammals is extremely complex and nitric oxide can be produced simultaneously, not just by many different nerve cells but also by the myriad of blood vessels that ramify throughout the brain. The aspect of brain function that we have selected to study in order to gain insights into the basics of nitric oxide biology is the control of movement, particularly the neural networks of the spinal cord that control locomotion and how these networks are controlled by the brainstem. We study the far simpler networks located in the central nervous system of young frog tadpoles which are assembled to regulate swimming movements. Our previous work in this area characterized nerve cells that can manufacture nitric oxide and these are located exclusively in the brainstem. In this project we wish to understand more about these nerve cells and characterize what other neurotransmitters they are able to make and release. The nitric oxide nerve cells belong to specific clusters which project to the spinal cord so it will be important to understand their activity during swimming and how they interact with each other in the presence or absence of nitric oxide. The nitric oxide produced in the brainstem acts on nerve cells of the spinal cord that generate movement, called motorneurons. Nitric oxide changes the electrical activity of motorneurons and hence how they respond to signals that tell the tadpole to swim, but how does nitric oxide achieve this 'modulation' of motorneurons and rhythmic movements for swimming? The advantages of studying nitric oxide signalling in the brain and spinal cord of this simple model system are numerous. Importantly the neural circuits that regulate locomotion bear many similarities to those of adult vertebrates, including mammals because they all derive from a common ancestry and are therefore built on a similar plan. In addition, the relative simplicity of the networks at early stages of development mean that nitric oxide effects can be studied at the level of single cells and understood in relation to the behaviour being regulated. From an ethical perspective it is advantageous to be able to study mechanisms of nitric oxide function that are highly conserved in an organism that does not possess the brain power to detect pain in the way that adult mammals like mice and cats do, if at all. Finally, the nitric oxide system is one of tremendous therapeutic importance and therefore our work may yield important clues as to how the system can be manipulated to the benefit of mankind in the future.

仅在20年前，人们才发现自由基气体一氧化氮是一种重要的生物信号分子，它控制着血管的直径。从那以后，人们发现一氧化氮在其他类型的组织中发挥着广泛的重要作用，包括调节神经细胞发育的大脑，以及许多大脑功能，如学习和记忆。一氧化氮是如何能够参与调节大脑几乎每个区域的电活动的，这仍然是一个谜。然而，我们知道某些神经细胞可以制造和释放一氧化氮，然后控制其他神经细胞相互交流的能力。在这方面很难取得进展的原因之一是，成年动物，尤其是哺乳动物的大脑极其复杂，一氧化氮不仅可以由许多不同的神经细胞同时产生，还可以由遍布大脑的无数血管同时产生。为了深入了解一氧化氮生物学的基础知识，我们选择研究的脑功能方面是运动的控制，特别是控制运动的脊髓神经网络以及这些网络是如何被脑干控制的。我们研究的是位于小蝌蚪中枢神经系统的更简单的网络，这些网络是用来调节游泳运动的。我们之前在这一领域的工作描述了可以制造一氧化氮的神经细胞，这些细胞只位于脑干中。在这个项目中，我们希望更多地了解这些神经细胞，并描述它们能够制造和释放的其他神经递质。一氧化氮神经细胞属于投射到脊髓的特定簇，因此了解它们在游泳时的活动以及它们在一氧化氮存在或不存在的情况下如何相互作用是很重要的。脑干中产生的一氧化氮作用于产生运动的脊髓神经细胞，称为运动神经元。一氧化氮会改变运动神经元的电活动，从而改变它们对蝌蚪游泳信号的反应，但一氧化氮是如何实现运动神经元的“调节”和有节奏的游泳运动的呢？在这个简单的模型系统中研究一氧化氮信号在大脑和脊髓中的优势是很多的。重要的是，调节运动的神经回路与成年脊椎动物（包括哺乳动物）有许多相似之处，因为它们都来自共同的祖先，因此建立在相似的计划上。此外，在发育的早期阶段，网络的相对简单意味着一氧化氮的作用可以在单个细胞的水平上进行研究，并理解与被调节的行为有关。从伦理的角度来看，能够研究一氧化氮功能机制是有利的，这种机制在一种生物中是高度保守的，这种生物不具备像老鼠和猫这样的成年哺乳动物那样感知疼痛的大脑能力，如果有的话。最后，一氧化氮系统是一个巨大的治疗重要性，因此我们的工作可能会提供重要的线索，如何操纵系统，以造福人类在未来。