Functional Modules in Primary Motor Cortex

传统的观点认为，身体的肌肉组织以一种体位的方式映射到运动皮层的表面（体位假说）。虽然粗糙的躯体解剖是一个不可否认的事实，但精细的功能分析一次又一次地表明，在不同的物种中，躯体解剖在较小的尺度上被破坏了。此外，覆盖长时间间隔的皮层内微刺激（ICMS）显示，运动皮层上的每个点都引发了复杂的、行为和病因相关的运动。这被解释为表示行为功能而不是基本运动（功能模块假说）。我们之前对啮齿动物初级须运动皮层（vM1）的研究表明，这两个区域彼此之间泾渭分明，是功能模块化组织的有力候选区域。在ICMS中，RW亚区引起有节奏的须状突起，而TZ引起须状突起收缩并伴有全身运动。只有TZ是体感觉皮层的靶区，而RW不是。在这个项目中，我们的目标是首先研究意志行为的两个候选模块中的每个模块的因果作用，需要在躯体解剖和功能模块假设之间做出决定。其次，我们的目标是找出这些假定模块所服务的行为功能和上下文。我们将首先表征候选模块的连通性，期望在模块的情况下找到定性的不同连接子集，或者在躯体解剖的情况下，在皮质表面上的基本投影模式的有序转移。在第二个和第三个目标中，整合在一个实验中，我们将在头部固定的小鼠中采用行为任务，旨在利用两个候选模块的假定功能，并使用光遗传沉默测试永久性病变和急性失活后各自的行为。这项任务将由两个部分组成，一个涉及在空气中搅拌（从而测试已知脑干模式发生器设定控制参数的假定功能），另一个涉及主动触摸，即搅拌对纹理的适应，以最大限度地区分。在这些不同的行为和感觉运动环境中，这两个区域的任何不同参与都会加强功能模块假说。

Classically it is held that the body's musculature is mapped in a somatotopic fashion across the surface of the motor cortex (somatotopy hypothesis). While a coarse somatotopy is an undeniable fact, finely resolved functional analysis has shown, time and again, and in different species, that the somatotopy is broken on the smaller scale. Moreover, intracortcal micro-stimulation (ICMS) covering long intervals revealed that each point on the motor cortex elicits complex, behaviorally and etiologically relevant movements. This has been interpreted to signify a representation of behavioral functions rather than elemental movements (functional modules hypothesis).Our own previous work in primary whisker motor cortex (vM1) of rodents revealed two areas sharply delineated from each other, and strong candidates for functional, modular organization. Upon ICMS, subarea RW elicits rhythmic whisking, while TZ elicits whisker retraction accompanied by whole body movements. Only TZ, not RW, is a target zone of somatosensory cortex. In this project our aim is to firstly study the causal role of each of the two candidate modules for volitional behavior, needed to decide between the somatotopy and functional module hypotheses. Secondly we aim to work out the behavioral functions and contexts served by these presumptive modules. We will first characterize the connectivity of the candidate modules, expecting to find qualitative different subsets of connections in the case of modules, or orderly shifts of a basic projection pattern across cortex surface in the case of somatotopy. In a second and third objective, integrated within one experiment, we will employ a behavioral task in head-fixed mice, designed to tap into presumed functions of the two candidate modules, and test the respective behavior after permanent lesions and acute deactivations using optogenetic silencing. The task will be comprised of two components, one involving whisking in air (thus testing the presumed function to set control parameters of a known brainstem pattern generator), and the other involving active touch, i.e adaptation of whisks against textures to maximize discrimination. Any differential involvement of the two areas in these different behaviors and sensorimotor contexts would strengthen the functional module hypothesis.