Towards elucidation of circuit mechanisms for feeding-related manual dexterity

项目摘要 灵巧的食物处理是一个关键的，但仍然知之甚少的基本运动行为类型。我们提出了一个 一项探索性的研究计划，研究老鼠如何使用它的手指和前爪灵巧地处理 食物初步结果表明，小鼠处理食物的运动，尽管看起来非常复杂， 可以分解为几种类型的简单元素，暂时确定为不同的，非常快速的 表现出部分定型和部分可变运动学特征的子运动。他们还建议， 老鼠的拇指（第一个手指，或D1; pollex）在灵巧中起着令人惊讶的大而先前未被认识的作用。 食物处理为了探索这些假设和观察结果，我们将首先开发一种方法， 表征自由移动小鼠的种子处理行为。为此，我们将使用高速，特写镜头的视频 捕获，结合深度神经网络方法进行自动无标记跟踪（DeepLabCut）。我们将 然后开发一种新的基于试验的范例，用于在更实验的情况下表征种子处理， 头部固定的受控条件。我们将联合收割机与光遗传学沉默工具相结合， 选择性靶向皮质区或运动皮质中选择性标记的皮质脊髓神经元，以及多- 探针/多通道线性阵列记录沿着感觉运动通路的关键节点中的尖峰活动。 总的来说，这项工作将促进我们对灵巧的机器人所涉及的基本运动的理解。 操纵食物，提供了新的见解，这一过程中，在一个基因听话的模式生物，和 为未来的研究开辟了道路，以解剖感觉运动回路介导特定的细胞机制， 前肢和手指运动控制方面。

PROJECT SUMMARY Dexterous food-handling is a critical but still poorly understood type of basic motor behavior. We propose an exploratory research program to investigate how the mouse uses its digits and forepaws to dexterously handle food. Preliminary results suggest that mouse food-handling movements, despite appearing extremely complex, can be decomposed into several types of simpler elements, tentatively identified as distinct and very rapid submovements that exhibit partly stereotyped and partly variable kinematic features. They also suggest that the mouse’s thumb (first digit, or D1; pollex) plays a surprisingly large and previously unrecognized role in dexterous food-handling. To explore these hypotheses and observations, we will first develop an approach for quantitatively characterizing seed-handling behaviors of freely moving mice. For this we will use high-speed, close-up video capture, combined with deep neural network methods for automated markerless tracking (DeepLabCut). We will then develop a novel trial-based paradigm for characterizing seed-handling under the more experimentally controlled conditions of head-fixation. We will combine this approach with tools for optogenetic silencing of either selectively targeted cortical areas or selectively labeled corticospinal neurons in motor cortex, as well as multi- probe/multi-channel linear array recordings of spiking activity in key nodes along sensorimotor pathways. Collectively this work will advance our understanding of the elemental movements involved in the dexterous manipulation of food, providing new insights into this process in a genetically tractable model organism, and opening the way for future studies to dissect the cellular mechanisms in sensorimotor circuits mediating specific aspects of forelimb and digit motor control.