Information processing by respiratory motoneurons

呼吸运动神经元的信息处理

• 批准号: RGPIN-2020-04835
• 负责人: Funk, Gregory
• 金额: $ 4.74万
• 依托单位: University of Alberta
• 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=763291
• 关键词: Information; processing; respiratory; motoneurons

Understanding how neurons transform input into output, i.e. how they integrate and process information, is fundamental to understanding brain function and how behaviour emerges from the activity of neural networks. Many neurons in the brain have multiple tasks. A major question in neuroscience is how are properties of neurons adjusted so that they can meet the diverse requirements of all these different tasks that are constantly changing. We study motoneurons of the tongue because they are easy to access, and because they play important roles in many different behaviours like breathing, suckling, swallowing, chewing, and even speech, so are well-suited for asking questions about how diverse responsibilities are managed. We will approach the problem from opposite ends of the behavioural spectrum. First, we will consider dreaming, or REM, sleep and explore mechanisms by which the brain essentially turns off motoneurons that control voluntary muscles, causing a type "paralysis" referred to as REM sleep atonia. This atonia is hypothesized to be protective in that it prevents us from acting out our dreams, but underlying mechanisms are not fully known and appear to differ between muscles, posing a question of fundamental importance. However, this question is also clinically relevant since loss of activity in the motoneurons that control the tongue during sleep is causally related to obstructive sleep apnea. Resolving the underlying mechanisms is important in the development of new treatments. At the other end of the spectrum we will explore how the complex branching structures (dendritic trees) of motoneurons through which they communicate with other neurons are organized to help them efficiently perform their different jobs. The geometry of the dendritic tree has long been recognized as a critical factor in determining how synaptic input is transformed into neuronal output, but how the brain utilizes the complex geometries of neurons to do this remains unclear. In this study we will use optical and electrophysiological methods that allow us to record from single motoneurons in brain slices from neonatal rodents that retain functioning neural networks that generate two rhythmic behaviours, breathing and suckling, in a dish. These endogenous behaviours are critical. It means that the connections from the breathing and suckling networks onto the motoneurons will be activated in a manner similar to what happens normally; i.e. we will monitor motor neuron activity while the breathing and suckling-related inputs are physiologically processed by the dendritic tree. Then, using optical methods to chemically turn off or excite different branches we will clarify the role of different dendrite branches in processing inspiratory and suckling inputs (i.e., do all dendrites have a similar role?). These experiments will provide new insight into neuronal integration and help clarify the basis for how the brain achieves such remarkable information processing.

了解神经元如何将输入转化为输出，即它们如何整合和处理信息，对于理解大脑功能以及行为如何从神经网络的活动中产生至关重要。大脑中的许多神经元有多种任务。神经科学中的一个主要问题是神经元的特性如何调整，以便它们能够满足所有这些不断变化的不同任务的不同要求。我们研究舌头的运动神经元是因为它们很容易接近，而且因为它们在呼吸、吮吸、吞咽、咀嚼甚至说话等许多不同的行为中起着重要的作用，所以它们非常适合询问如何管理不同的责任。我们将从行为光谱的两端来处理这个问题。首先，我们将考虑做梦或REM睡眠，并探索大脑基本上关闭控制随意肌的运动神经元的机制，导致一种称为REM睡眠张力不足的“瘫痪”。这种弛缓被认为是保护性的，因为它阻止我们把梦表现出来，但其潜在的机制还不完全清楚，而且似乎在肌肉之间存在差异，这就提出了一个至关重要的问题。然而，这个问题也是临床相关的，因为在睡眠期间控制舌头的运动神经元的活动丧失与阻塞性睡眠呼吸暂停有因果关系。解决潜在的机制对于开发新的治疗方法非常重要。在光谱的另一端，我们将探索运动神经元的复杂分支结构（树突树）如何组织它们与其他神经元进行通信，以帮助它们有效地执行不同的工作。树突树的几何形状一直被认为是决定突触输入如何转化为神经元输出的关键因素，但大脑如何利用神经元的复杂几何形状来实现这一点仍然不清楚。在这项研究中，我们将使用光学和电生理学方法，使我们能够记录来自新生啮齿动物脑切片中的单个运动神经元，这些新生啮齿动物保留了功能正常的神经网络，这些神经网络在培养皿中产生两种有节奏的行为，呼吸和吮吸。这些内生行为至关重要。这意味着从呼吸和吮吸网络到运动神经元的连接将以类似于正常情况下发生的方式被激活;也就是说，我们将监测运动神经元的活动，而呼吸和吮吸相关的输入则由树突树进行生理处理。然后，使用光学方法来化学关闭或激发不同的分支，我们将阐明不同树突分支在处理吸气和吮吸输入中的作用（即，所有的树突都有类似的作用吗？）。这些实验将为神经元整合提供新的见解，并有助于阐明大脑如何实现如此卓越的信息处理的基础。