The functional organization of motor cortex: a multilevel analysis

运动皮层的功能组织：多层次分析

• 批准号: RGPIN-2019-04140
• 负责人: Teskey, Gordon
• 金额: $ 3.42万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714658
• 关键词: functional; organization; motor; cortex; multilevel

Early researchers studying the function of motor cortex initially thought it was a homogenous structure. But my laboratory and others have shown this is not the case. To begin, we asked, "what is the function of motor cortex"? The traditional response is that motor cortex serves to make individual muscles twitch. Yet this long-standing view was based upon experimentation with short-duration stimulation trains (40 ms) that are only capable of eliciting individual muscle twitches. My laboratory recently adopted long-duration stimulation trains that last for the same amount of time it takes to make a purposeful movement. We discovered that there are subsets of highly reproducible and robust reaching movement patterns across the surface of motor cortex. We have named these forelimb reaching areas: elevate, advance, grasp and retract. We then observed that temporarily inactivating the "grasp" region results in deficits in grasping behaviour. This is important because our evidence supports the view that the motor cortex is organized to make purposeful multi-joint movements rather than simple muscle twitches. Thus, our general hypothesis is that the motor cortex is primarily organized around purposeful multi-joint movements. I will advance our knowledge of motor learning and memory by examining 4 objectives; Objective 1 will derive the motor map of multi-joint movements during development and then determine the effects of rearing environment and skilled learning on the movement representations. Objective 2 will determine the role of various sub-areas of multi-joint forelimb movements (elevate, advance, retract) on motor performance and motor learning using cortical cooling in adult rats. Objective 3 will determine the intrinsic and extrinsic anatomical connections underpinning the various multi-joint movement categories in the adult rat. Objective 4 will determine the contribution of the transient receptor potential (TRP) channels on motor learning, the expression of motor representations and layer V pyramidal cell excitability. Thus, I propose to analyze the functioning of motor cortex at four inter-related levels of analysis; a) behaviour of the forelimb, b) motor representations (motor maps) of the forelimb primarily using long-duration intracortical microstimulation which gives rise to multi-joint movement motor maps, c) intrinsic and extrinsic anatomy and d) synaptic ligands and channels using an in vitro slice preparation that my laboratory developed. Significance: The motor cortex is tractable for understanding how the brain regulates complex behaviour. Delineating the network, synaptic and channel properties that underlie the organization of motor cortex will improve our understanding of the fundamental processes that regulate behaviour.

早期研究运动皮质功能的研究人员最初认为它是一种同质结构。但我的实验室和其他人已经证明，情况并非如此。一开始，我们问：“运动皮质的功能是什么？”传统的反应是，运动皮质用于使个别肌肉抽搐。然而，这一由来已久的观点是基于对短时刺激序列(40ms)的实验，这种刺激序列只能引发个别肌肉抽动。我的实验室最近采用了长持续时间的刺激训练，持续的时间与进行有目的的运动所需的时间相同。我们发现，在运动皮质表面有一些高度可重复性和健壮的到达运动模式的子集。我们将这些前肢到达的区域命名为：抬高、前进、抓取和后退。然后，我们观察到，暂时使“抓握”区域失活会导致抓握行为的缺陷。这一点很重要，因为我们的证据支持这样的观点，即运动皮质的组织是为了进行有目的的多关节运动，而不是简单的肌肉抽搐。因此，我们的一般假设是，运动皮质主要是围绕着有目的的多关节运动来组织的。 我将通过检查四个目标来提高我们对运动学习和记忆的认识； 目标1将获得发育过程中多关节运动的运动图，然后确定养育环境和熟练学习对运动表征的影响。 目的2研究多关节前肢运动的不同亚区(抬起、前移、后退)对成年大鼠运动能力和运动学习的影响。 目标3将确定支持成年大鼠各种多关节运动类别的内在和外在解剖学联系。 目的4确定瞬时受体电位(TRP)通道在运动学习、运动表征的表达和V层锥体细胞兴奋性中的作用。 因此，我建议在四个相互关联的分析水平上分析运动皮质的功能：a)前肢的行为，b)前肢的运动表征(运动图)，主要使用长时间皮质内微刺激产生多关节运动运动图，c)内在和外部解剖学，以及d)使用我实验室开发的体外切片制备的突触配体和通道。 意义：运动皮质很容易理解大脑是如何调节复杂行为的。描绘作为运动皮质组织基础的网络、突触和通道属性，将提高我们对调节行为的基本过程的理解。