Khanal Nischal, Padawer-Curry Jonah A, Voss Trevor, Schulte Kevin A, Bice Annie R, Bauer Adam Q
Imaging Science Program, Washington University in St. Louis, St. Louis, Missouri, United States; Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, 660 S. Euclid Ave, St. Louis, MO 63110, United States.
Biophotonics Center, School of Engineering, Vanderbilt University, Keck FEL Center, Suite 200, 410 24th Ave. South, Nashville, TN 37232, United States.
Brain Stimul. 2024 Nov-Dec;17(6):1229-1240. doi: 10.1016/j.brs.2024.10.010. Epub 2024 Oct 29.
Motor mapping allows for determining the macroscopic organization of motor circuits and corresponding motor movement representations on the cortex. Techniques such as intracortical microstimulation (ICMS) are robust, but can be time consuming and invasive, making them non-ideal for cortex-wide mapping or longitudinal studies. In contrast, optogenetic motor mapping offers a rapid and minimally invasive technique, enabling mapping with high spatiotemporal resolution. However, motor mapping has seen limited use in tracking 3-dimensonal, multi-limb movements in awake animals. This gap has left open questions regarding the underlying organizational principles of motor control of coordinated, ethologically-relevant movements involving multiple limbs.
Our first objective was to develop Multi-limb Optogenetic Motor Mapping (MOMM) to concurrently map motor movement representations of multiple limbs with high fidelity in awake mice. Having established MOMM, our next objective was determine whether maps of coordinated and ethologically-relevant motor output were topographically organized on the cortex.
We combine optogenetic stimulation with a deep learning driven pose-estimation toolbox, DeepLabCut (DLC), and 3-dimensional triangulation to concurrently map motor movements of multiple limbs in awake mice.
MOMM consistently revealed cortical topographies for all mapped features within and across mice. Many motor maps overlapped and were topographically similar. Several motor movement representations extended beyond cytoarchitecturally defined somatomotor cortex. Finer articulations of the forepaw resided within gross motor movement representations of the forelimb. Moreover, many cortical sites exhibited concurrent limb coactivation when photostimulated, prompting the identification of several cortical regions harboring coordinated and ethologically-relevant movements.
The cortex appears to be topographically organized by motor programs, which are responsible for coordinated, multi-limbed, and behavior-like movements.
运动图谱有助于确定运动回路的宏观组织以及皮层上相应的运动表征。诸如皮层内微刺激(ICMS)等技术很可靠,但可能耗时且具有侵入性,使其不适用于全皮层图谱绘制或纵向研究。相比之下,光遗传学运动图谱提供了一种快速且微创的技术,能够以高时空分辨率进行图谱绘制。然而,运动图谱在追踪清醒动物的三维多肢体运动方面的应用有限。这一差距使得关于涉及多个肢体的协调、与行为学相关运动的运动控制潜在组织原则的问题悬而未决。
我们的首要目标是开发多肢体光遗传学运动图谱(MOMM),以便在清醒小鼠中同时以高保真度绘制多个肢体的运动表征。在建立了MOMM之后,我们的下一个目标是确定协调的、与行为学相关的运动输出图谱在皮层上是否具有拓扑组织。
我们将光遗传学刺激与深度学习驱动的姿态估计工具箱DeepLabCut(DLC)以及三维三角测量相结合,以同时绘制清醒小鼠多个肢体的运动。
MOMM始终揭示了小鼠内部和之间所有映射特征的皮层拓扑结构。许多运动图谱相互重叠且在拓扑上相似。几个运动表征超出了细胞结构定义的躯体运动皮层。前爪更精细的关节活动位于前肢的总体运动表征之内。此外,许多皮层部位在光刺激时表现出同时的肢体共同激活,从而促使识别出几个包含协调的、与行为学相关运动的皮层区域。
皮层似乎由运动程序进行拓扑组织,这些运动程序负责协调的、多肢体的和类似行为的运动。