The functional organization of motor cortex: a multilevel analysis

早期研究运动皮层功能的研究人员最初认为它是一个同质结构。但我的实验室和其他人的研究表明，情况并非如此。首先，我们问，“运动皮层的功能是什么？”传统的反应是运动皮层使单个肌肉抽搐。然而，这种长期存在的观点是基于短时间刺激训练（40毫秒）的实验，这种训练只能引起单个肌肉的抽搐。我的实验室最近采用了长时间的刺激训练，持续的时间与做一个有目的的动作所需的时间相同。我们发现，在运动皮层的表面上有一些高度可重复的、强大的到达运动模式。我们将这些前肢到达区域命名为：提升、前进、抓握和收缩。然后我们观察到，暂时关闭“抓握”区域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一种观点，即运动皮层是有组织地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，运动皮层主要是围绕有目的的多关节运动组织的。我将通过考察4个目标来推进我们对运动学习和记忆的认识；目的1推导发育过程中多关节运动的运动图，确定饲养环境和技能学习对运动表征的影响。目的2将通过皮质冷却确定成年大鼠多关节前肢运动的不同亚区（提升、前进、收缩）对运动表现和运动学习的作用。目的3将确定成年大鼠各种多关节运动类别的内在和外在解剖连接。目的4将确定瞬时受体电位（TRP）通道对运动学习、运动表征的表达和V层锥体细胞兴奋性的贡献。因此，我建议在四个相互关联的分析水平上分析运动皮层的功能；A)前肢的行为，b)主要使用长时间的皮质内微刺激产生多关节运动运动图的前肢的运动表征（运动图），c)内在和外在解剖，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：运动皮层对于理解大脑如何调节复杂行为是容易处理的。描绘运动皮层组织背后的网络、突触和通道特性，将提高我们对调节行为的基本过程的理解。

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.