Thalamocortical control of skilled motor behaviour

丘脑皮质对熟练运动行为的控制

基本信息

批准号：
BB/R018537/1
负责人：
Ian Duguid
金额：
$ 50.18万
依托单位：
University of Edinburgh
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FR018537%2F1
关键词：
Thalamocortical control skilled motor behaviour

项目摘要

Motor control is a basic but fundamentally important aspect of human and animal behaviour and the only we way interact with the world is though movement. Thus, one of the most challenging problems in neuroscience is to understand how the brain generates and controls motor behaviour. Over the past century significant advances have been made in understanding how descending information from cortical and brainstem motor areas regulate spinal cord activity in order to execute a wide range of motor tasks from simple rhythmic behaviours to complex, dexterous tasks such as reaching and object manipulation. One pathway that is pivotal to the preparation and execution of a large repertoire of learned, dextrous movements is the basal ganglia-thalamcortical pathway. This pathway is thought to convey motivational and/or contextual information from the basal ganglia via thalamus to the primary motor cortex in order to select, prepare and execute different motor behaviours. Disruption to information transmission along this pathway leads to severe motor deficits and loss of motor control. Although we have an in-depth understanding of how basal ganglia-thalamocortical activity correlates with specific aspects of mammalian motor behaviour, the vast majority of these data have been generated using extracellular recording methods that preclude measurement of somatodendritic integration, input-output transformations, connection specific dynamics and spatiotemporal mapping of activity patterns across neuronal ensembles. This leads us to question, what are the spatiotemporal activity patterns of thalamocortical inputs in primary motor cortex (M1) during movement preparation/execution/suppression? How do these inputs shape somatodendritic integration in layer 5 projection neurons in M1 during behaviour? What is the causal link between activity along the basal ganglia-thalamocortical pathway, M1 output and behaviour?To address these questions, we will investigate the neural representations of movement in M1 in mice trained to execute an auditory cued Go/NoGo forelimb push task developed in our lab. This behavioural paradigm is of particular interest as it provides an experimentally tractable model of complex motor control and facilitates the use of in vivo 2-photon calcium imaging, whole-cell patch-clamp electrophysiology and cell-selective opto-/chemogenetic manipulation techniques in head-restrained mice. By combining state-of-the-art cellular and circuit approaches in vivo, we will investigate the importance of the basal ganglia-thalamocortical input pathway in shaping M1 layer 5 projection neuron somatodendritic computations during behaviour. Given that axons from the basal ganglia-recipient area of motor thalamus (MThBG) primarily target the apical dendrites of layer 5 projection neurons in M1 and that behaviour-related MThBG activity precedes movement initiation, we will test the hypothesis that motor thalamocortical axons from MThBG (mTCBG) drive task context-specific modulation of dendritic activity and layer 5 output during movement preparation. We will also use cell- and pathway-specific opto-/chemogenetic manipulation strategies to determine the causal relationship between mTCBG activity, layer 5 somatodendritic computations and movement planning/execution. The overarching aim of the project is to provide new insights into the importance of M1 cellular and circuit computations during the execution of a learned, dextrous motor task, serving as an exemplar for the development of a more general mechanistic understanding of cortical motor control.

运动控制是人类和动物行为的一个基本但至关重要的方面，我们与世界互动的唯一方式就是运动。因此，神经科学中最具挑战性的问题之一是了解大脑如何产生和控制运动行为。在过去的一个世纪里，在理解来自皮层和脑干运动区的下行信息如何调节脊髓活动以执行各种运动任务（从简单的节律行为到复杂、灵巧的任务（例如伸手和物体操作））方面取得了重大进展。对于准备和执行大量习得的灵巧动作至关重要的一条通路是基底神经节-丘脑皮层通路。该通路被认为将动机和/或背景信息从基底神经节通过丘脑传递到初级运动皮层，以便选择、准备和执行不同的运动行为。沿着这条通路的信息传输中断会导致严重的运动缺陷和运动控制丧失。尽管我们对基底神经节-丘脑皮层活动如何与哺乳动物运动行为的特定方面相关有深入的了解，但绝大多数数据是使用细胞外记录方法生成的，这些方法排除了体树突整合、输入输出转换、连接的测量跨神经元集合的活动模式的特定动力学和时空映射。这让我们产生疑问，在运动准备/执行/抑制期间，初级运动皮层（M1）丘脑皮层输入的时空活动模式是什么？这些输入如何在行为过程中塑造 M1 中第 5 层投射神经元的体树突整合？基底神经节-丘脑皮质通路的活动、M1 输出和行为之间的因果关系是什么？为了解决这些问题，我们将研究经过训练以执行听觉提示 Go/NoGo 前肢推动任务的小鼠 M1 运动的神经表征在我们的实验室。这种行为范式特别令人感兴趣，因为它提供了复杂运动控制的实验上易于处理的模型，并促进了体内 2 光子钙成像、全细胞膜片钳电生理学和细胞选择性光/化学遗传学操纵技术在头部的使用- 抑制老鼠。通过结合体内最先进的细胞和电路方法，我们将研究基底神经节-丘脑皮质输入通路在行为过程中塑造 M1 层 5 投影神经元体树突计算中的重要性。鉴于来自运动丘脑基底神经节受体区 (MThBG) 的轴突主要针对 M1 中第 5 层投射神经元的顶端树突，并且与行为相关的 MThBG 活动先于运动启动，我们将检验来自 MThBG 的运动丘脑皮质轴突的假设(mTCBG) 在运动准备期间驱动树突活动和第 5 层输出的任务上下文特定调制。我们还将使用细胞和通路特异性的光/化学遗传学操作策略来确定 mTCBG 活性、第 5 层体细胞树突计算和运动计划/执行之间的因果关系。该项目的总体目标是提供关于 M1 细胞和电路计算在执行学习的、灵巧的运动任务期间的重要性的新见解，作为发展对皮质运动控制更普遍的机械理解的范例。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cerebellar-recipient motor thalamus drives behavioral context-specific movement initiation

DOI：
10.1101/802124
发表时间：
2019-01-01
期刊：
bioRxiv
影响因子：
0
作者：
Dacre, J.
通讯作者：
Dacre, J.

A cranial implant for stabilizing whole-cell patch-clamp recordings in behaving rodents.

DOI：
10.1016/j.jneumeth.2023.109827
发表时间：
2023-04-15
期刊：
JOURNAL OF NEUROSCIENCE METHODS
影响因子：
3
作者：
Dacre, Joshua;Rivera, Michelle Sanchez;Schiemann, Julia J.;Currie, Stephen;Ammer, Julian J.;Duguid, Ian
通讯作者：
Duguid, Ian

Movement-specific signaling is differentially distributed across motor cortex layer 5 projection neuron classes.

DOI：
10.1016/j.celrep.2022.110801
发表时间：
2022-05-10
期刊：
CELL REPORTS
影响因子：
8.8
作者：
Currie, Stephen P.;Ammer, Julian J.;Premchand, Brian;Dacre, Joshua;Wu, Yufei;Eleftheriou, Constantinos;Colligan, Matt;Clarke, Thomas;Mitchell, Leah;Faisal, A. Aldo;Hennig, Matthias H.;Duguid, Ian
通讯作者：
Duguid, Ian

A cerebellar-thalamocortical pathway drives behavioral context-dependent movement initiation.

小脑-丘脑皮质通路驱动行为环境相关的运动启动。

DOI：
10.1016/j.neuron.2021.05.016
发表时间：
2021-07-21
期刊：
Neuron
影响因子：
16.2
作者：
Dacre J;Colligan M;Clarke T;Ammer JJ;Schiemann J;Chamosa-Pino V;Claudi F;Harston JA;Eleftheriou C;Pakan JMP;Huang CC;Hantman AW;Rochefort NL;Duguid I
通讯作者：
Duguid I

Cerebellar-recipient motor thalamus drives behavioural context-specific movement initiation

小脑接收运动丘脑驱动行为特定的运动启动