Temporal dissection of the grasping circuit

系统神经科学的一个终极目标是解释基于大脑活动的人类行为。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交谈和相互作用的。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，它们的大脑有更多不同的区域。此外，了解不同大脑区域是如何相互作用的，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神经元的活动，结合新颖和复杂的分析，提供了一个前所未有的机会来促进我们对大脑区域之间的相互作用如何影响行为的理解。在这个项目中，我们将研究控制视觉引导抓取的大脑网络中的相互作用。GRASH网络是研究不同大脑区域之间相互作用的更广泛问题的理想模型系统。我们可以实现对这个系统的输入(要抓住的物体的视觉)的精细、毫秒级的控制，也可以同样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很重要，因为手的功能是日常生活的基础，对于我们的技术、交流、文化和社交来说，手功能的丧失是毁灭性的。我们将把注意力集中在负责抓取的大脑网络的三个关键节点上：两个半球(运动前区域)的初级运动皮质和次级运动皮质，它们都是关键的参与，并在视觉引导的抓取过程中相互作用。就我们所知，这些区域之间的相互作用从来没有同时被调查过。因此，我们仍然缺乏对抓握如何在时间上准确展开的了解，从第一次看到物体到手的预先成形，再到实际的抓取，以及抓取大脑区域之间的相互作用是如何影响抓取的。我们将记录抓取过程中数千个神经元的活动，并应用最先进的分析技术来发现大脑区域如何相互交谈来实现这种复杂的运动行为。为了了解大脑相互作用在掌握行为中的因果作用，我们将使用专门设计的行为任务以及药物和光遗传干扰技术来操纵行为和大脑活动。在这个项目中，我们将揭示灵长类大脑中多个空间分布的区域如何协作实现特定行为的基本原理，这对神经通信理论至关重要。我们将提供对在抓握过程中控制我们双手的神经机制的见解，对于理解大脑对健康和疾病中人类手功能的控制具有重要意义。

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.