Glial cell involvement in spinal motor control: cheering from the side-lines or part of the team?

神经胶质细胞参与脊髓运动控制：从场边还是团队的一部分欢呼？

• 批准号: BB/M021793/1
• 负责人: Gareth Miles
• 金额: $ 64.41万
• 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: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM021793%2F1
• 关键词: Glial; cell; involvement; spinal; motor

Research investigating the function of the brain and spinal cord (central nervous system) typically focuses on the role of nerve cells. However, recent work suggests that other cells, called glial cells, also control brain activity and therefore behaviour. Furthermore, the dysfunction of glial cells is known to be involved in many disorders of the central nervous system. Given the potential importance of glial cells in both health and disease, and the lack of widespread acceptance that glial cells are more than just 'support cells', we aim to provide clear evidence of involvement of glial cells in the control of neural networks and ultimately behaviour. We will achieve this by studying the role of glial cells in neural networks of the spinal cord which control movement. We have chosen networks of the spinal cord because, unlike most networks in the brain, they are relatively well-defined and we know and can measure the behaviour they control.Our research will involve the use of state-of-the-art genetic, physiological and imaging techniques that allow us to measure the activity of neurons and glial cells and study their interactions. Using isolated pieces of mouse spinal cord we will first define the mechanisms of bi-directional signalling between glial cells and neurons. We will then examine the effect that glia to neuron signalling has on the network of neurons in the spinal cord which controls walking. This network can be studied using isolated mouse spinal cord tissue which can generate the electrical signals that control walking even when 'in a dish'. Next, we will study glia to neuron signalling in human cells. We will use new technology which allows stem cells to be derived from human skin samples. These stem cells can then be turned into glial cells and spinal neurons which can be grown together and studied in the lab. By defining the ways in which glial cells and neurons of the spinal cord communicate and the effect this signalling has on neural networks that control movement, we will provide important new information about the role of glial cells in the generation of central nervous system activity and ultimately the control of behaviour. In addition, given that many diseases of the brain and spinal cord involve glial cells, the basic knowledge we generate about the function of glial cells (in mice and importantly also humans) will be critical for future studies targeting glial cells to design new treatments for a range of diseases.

研究大脑和脊髓(中枢神经系统)功能的研究通常侧重于神经细胞的作用。然而，最近的研究表明，其他被称为胶质细胞的细胞也控制着大脑的活动，因此也控制着行为。此外，神经胶质细胞的功能障碍被认为与许多中枢神经系统的紊乱有关。鉴于神经胶质细胞在健康和疾病中的潜在重要性，以及缺乏广泛接受的神经胶质细胞不仅仅是“支持细胞”的观点，我们的目标是提供明确的证据，证明神经胶质细胞参与控制神经网络和最终的行为。我们将通过研究神经胶质细胞在控制运动的脊髓神经网络中的作用来实现这一点。我们之所以选择脊髓网络，是因为与大脑中的大多数网络不同，它们定义相对明确，我们知道并可以测量它们控制的行为。我们的研究将涉及使用最先进的遗传、生理和成像技术，使我们能够测量神经元和神经胶质细胞的活动，并研究它们之间的相互作用。利用分离的小鼠脊髓片段，我们将首先确定神经胶质细胞和神经元之间双向信号传递的机制。然后，我们将研究神经胶质细胞到神经元的信号传递对控制行走的脊髓神经元网络的影响。这种网络可以用分离的小鼠脊髓组织来研究，这种组织可以产生控制行走的电信号，即使是在“盘子里”。接下来，我们将研究人类细胞中的神经胶质细胞到神经元的信号传递。我们将使用新技术，允许从人类皮肤样本中提取干细胞。然后，这些干细胞可以转化为神经胶质细胞和脊髓神经元，可以一起生长并在实验室进行研究。通过定义神经胶质细胞和脊髓神经元的沟通方式，以及这种信号对控制运动的神经网络的影响，我们将提供有关神经胶质细胞在中枢神经系统活动的产生和最终行为控制中所起作用的重要新信息。此外，考虑到许多大脑和脊髓疾病涉及神经胶质细胞，我们对神经胶质细胞(在小鼠身上，更重要的是在人类中)功能的基本知识将对未来针对神经胶质细胞的研究至关重要，以设计针对一系列疾病的新疗法。

项目成果

Mapping synapses and astrocytic processes in the mammalian spinal cord

绘制哺乳动物脊髓中的突触和星形胶质细胞过程

• 发表时间: 2017
• 作者: Broadhead MJ

Movement-related activity in the periarcuate cortex of monkeys during coordinated eye and hand movements

• DOI: 10.1152/jn.00279.2017
• 发表时间: 2017-12-01
• 期刊: JOURNAL OF NEUROPHYSIOLOGY
• 影响因子: 2.5
• 作者: Kurata, Kiyoshi

Localization of muscarinic acetylcholine receptor-dependent rhythm-generating modules in the Drosophila larval locomotor network.

毒蕈碱乙酰胆碱受体依赖性节奏模块在果蝇幼虫运动网络中的定位。

• DOI: 10.1152/jn.00106.2021
• 发表时间: 2022-04-01
• 期刊: Journal of neurophysiology
• 影响因子: 2.5

Neural-glial communication in the mammalian spinal cord modulates locomotor networks

哺乳动物脊髓中的神经胶质细胞通讯调节运动网络

• 发表时间: 2018
• 作者: Broadhead MJ