Information processing by respiratory motoneurons

理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，是理解大脑功能和行为如何从神经网络活动中产生的基础。大脑中的许多神经元都有多重任务。神经科学的一个主要问题是如何调整神经元的特性，使它们能够满足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，因为它们很容易接近，因为它们在许多不同的行为中起着重要的作用，比如呼吸、哺乳、吞咽、咀嚼，甚至说话，所以它们非常适合研究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，我们将考虑做梦或快速眼动睡眠，并探索大脑本质上关闭控制随意肌的运动神经元的机制，从而导致一种被称为快速眼动睡眠弛缓症的“瘫痪”。这种张力失调被认为是一种保护作用，因为它可以防止我们把梦表演出来，但潜在的机制尚不完全清楚，而且似乎不同肌肉之间存在差异，这提出了一个至关重要的问题。然而，这个问题也与临床相关，因为睡眠中控制舌头的运动神经元活动的丧失与阻塞性睡眠呼吸暂停有因果关系。解决潜在的机制对开发新的治疗方法很重要。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）是如何组织起来的，通过它们与其他神经元进行交流，帮助它们有效地完成不同的工作。长期以来，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目标仍不清楚。在这项研究中，我们将使用光学和电生理学方法，使我们能够记录新生啮齿动物大脑切片中的单个运动神经元，这些啮齿动物保留了在培养皿中产生两种节律行为（呼吸和哺乳）的功能神经网络。这些内生行为至关重要。这意味着从呼吸和哺乳网络到运动神经元的连接将以与正常情况相似的方式被激活；也就是说，当呼吸和哺乳相关的输入由树突树进行生理处理时，我们将监测运动神经元的活动。然后，使用光学方法来化学关闭或激发不同的分支，我们将澄清不同的树突分支在处理吸入和吮吸输入中的作用（即，所有的树突都有相似的作用吗？）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。

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.