Information processing by respiratory motoneurons

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，是理解大脑功能和行为如何从神经网络活动中出现的基础。大脑中的许多神经元有多项任务。神经科学中的一个主要问题是，如何调整神经元的属性，使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触到，而且因为它们在许多不同的行为中扮演着重要的角色，比如呼吸、哺乳、吞咽、咀嚼，甚至是说话，所以非常适合于提出关于如何管理不同职责的问题。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肉的运动神经元的机制，从而导致一种被称为快速眼动睡眠张力的“麻痹”类型。这种紧张症被认为是保护性的，因为它阻止我们实现我们的梦想，但潜在的机制并不完全清楚，而且似乎在肌肉之间有所不同，这提出了一个根本的重要问题。然而，这个问题在临床上也是相关的，因为睡眠期间控制舌头的运动神经元失去活动与阻塞性睡眠呼吸暂停有关。解决潜在的机制在开发新的治疗方法方面很重要。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)是如何组织的，它们通过这些结构与其他神经元进行交流，以帮助它们有效地执行不同的工作。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，但大脑如何利用复杂的神经元几何形状来实现这一点仍不清楚。在这项研究中，我们将使用光学和电生理学方法，允许我们从新生啮齿动物脑片中的单个运动神经元进行记录，这些神经元保留了在一个碟子中产生两种节奏行为的神经网络，呼吸和哺乳。这些内生行为是至关重要的。这意味着从呼吸和哺乳网络到运动神经元的连接将以类似正常发生的方式被激活；即，我们将监测运动神经元的活动，而与呼吸和哺乳相关的输入由树突树进行生理处理。然后，使用光学方法化学地关闭或兴奋不同的树枝，我们将阐明不同的树突分支在处理吸气和哺乳输入中的作用(即，所有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非凡的信息处理的基础。

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.