Temporal dissection of the grasping circuit

系统神经科学的终极目标是根据大脑活动来解释人类行为。越来越清楚的是，为了做到这一点，我们需要了解不同的大脑区域是如何相互交流和互动的。灵长类动物（包括人类）的大脑尤其如此，与老鼠等低等哺乳动物相比，灵长类动物的大脑有更多不同的区域。此外，了解不同大脑区域如何相互作用可能对未来人类大脑疾病的诊断和治疗很重要。新的实验技术允许在行为过程中同时监测不同大脑区域中数千个单个神经元的活动，结合新颖而复杂的分析，为我们了解大脑区域之间的相互作用如何影响行为提供了前所未有的机会。在这个项目中，我们将研究大脑网络中控制视觉引导抓取的相互作用。抓取网络是一个理想的模型系统，用于研究不同大脑区域之间的相互作用。我们可以对这个系统的输入（要抓住的物体的视觉）实现精确到毫秒的控制，同样也可以很容易地描述网络输出（手部运动学和肌肉活动）。理解抓握的视觉控制是很重要的，因为手的功能是日常生活的基础，对于我们的科技、交流、文化和社会互动来说，失去手的功能是毁灭性的。我们将重点关注大脑网络中负责抓取的三个关键节点：两个半球的初级运动皮层和次级运动皮层（运动前区），它们在视觉引导的抓取过程中都至关重要并相互作用。据我们所知，这些领域之间的相互作用从未同时被研究过。因此，对于从第一眼看到一个物体到手预先塑造到实际的抓握，以及它是如何受到抓握大脑区域之间相互作用的影响，人们仍然缺乏理解。我们将记录数千个单个神经元在抓取过程中的活动，并应用最先进的分析技术来发现大脑区域如何相互交流以实现这种复杂的运动行为。为了理解大脑相互作用在抓取行为中的因果作用，我们将使用专门设计的行为任务以及药理学和光遗传干扰技术来操纵行为和大脑活动。在这个项目中，我们将揭示灵长类动物大脑中多个空间分布区域如何协作以实现特定行为的基本原理，这对神经通信理论至关重要。我们将提供在抓握过程中控制我们手的神经机制的见解，这对理解大脑控制人类手在健康和疾病中的功能具有重要意义。

An ultimate goal of systems neuroscience is to explain human behaviour based on brain activity. It is becoming increasingly clear that in order to do this we need to understand how different brain areas talk and interact with each other. This is especially true for the brains of primates (including humans), which have many more distinct areas compared to lower mammals, such as the mouse. Moreover, understanding how different brain areas interact is likely to be important in the future for the diagnosis and treatment of human brain disorders. New experimental techniques that allow simultaneous monitoring of the activity of thousands of individual neurons in different brain areas during behaviour combined with novel and sophisticated analysis provide an unprecedented opportunity to advance our understanding of how interactions between brain areas contribute to behaviour.In this project, we will investigate interactions in the brain network controlling visually guided grasping. The grasp network is an ideal model system to examine wider issues of interactions between different brain areas. We can achieve exquisite, millisecond-precise control of this system's input (vision of an object to be grasped), and can likewise easily characterise the network output (hand kinematics and muscle activity). Understanding visual control of grasp is important because hand function is fundamental to daily life, for our technology, communication, culture and social interaction, and loss of hand function is devastating. We will focus our attention on three key nodes of the brain network responsible for grasping: the primary motor cortex and the secondary motor cortices in both hemispheres (premotor areas) which are all critically involved and interact during visually guided grasp. To the best of our knowledge, interactions between these areas have never been investigated simultaneously. Therefore, there is still a lack of understanding of how precisely grasping unfolds in time, from the first sight of an object through hand pre-shaping to the actual grasp and how it is influenced by interactions between grasping brain areas.We will record the activity of thousands of individual neurons during grasp and apply state-of-the-art analysis techniques to discover how brain areas talk to each other to enable this complex motor behaviour. To understand the causal role of brain interactions in grasping behaviour, we will manipulate behaviour and brain activity using a specifically designed behavioural task and pharmacological and optogenetic interference techniques.In this project, we will reveal fundamental principles of how multiple, spatially distributed areas in the primate brain collaborate to achieve a specific behaviour, this is critical for theories of neural communication. We will provide insights into neural mechanisms controlling our hands during grasp, with important implications for understanding brain control of human hand function in health and disease.