Analysis of spinal locomotor circuit development in the little skate Leucoraja erinacea

运动是一种基本的和至关重要的动物行为，它依赖于动物的活动。 存在于脑干和脊髓内的不同神经元类别。脊髓运动神经元 在协调运动行为方面发挥核心作用，并受到当地网络的参与 促进肢体肌肉激活的节奏和模式的中间神经元。基本遗传 控制脊髓中间神经元和运动神经元之间连接的程序 这在很大程度上是由于数百个肌肉群的复杂性， 脊髓运动回路在这一探索性提案中，我们将评估其组成， 小冰鞋Leucoraja erinacea运动回路的连接性，一种原始的软骨 行走行为与四足动物非常相似的鱼。值得注意的是， 发现Leucoraja中支配鳍的运动神经元的分子谱几乎是 与四足动物的相同。Leucoraja产生双足运动使用8解剖学 轮廓分明的腹鳍肌肉，尽管产生这种行为的神经回路 没有特征的在这个建议中，我们将确定的子类型身份和连接 Leocoraja的脊髓运动神经元、中间神经元和肌肉。我们还将探讨 Leucoraja用于使用病毒跨突触追踪评估运动回路连接程序 分析和电生理学。在目标1中，我们将评估电路组成和连接性 Leucoraja运动神经元和中间神经元，并探讨通过Hox的作用信号 转录因子在柱状和池型运动神经元区域分布中的作用 身份在Aim 2中，我们将使用病毒追踪测定来确定连接模式 脊髓中间神经元和运动神经元之间的联系，并探索脊髓内神经元的运作。 中央模式发生器（CPG），在行走过程中协调鳍肌的激活 还有游泳通过利用这种原始的相对简单的神经肌肉组织结构， 脊椎动物，并建立我们在深入了解神经规范程序在 哺乳动物脊髓，这些研究可以提供深入了解的基本机制， 组装哪些电机电路。

Locomotion is a fundamental and vital animal behavior which relies on the activities of diverse neuronal classes residing within the brainstem and spinal cord. Spinal motor neurons play a central role in coordinating locomotor behaviors, and are engaged by networks of local interneurons that facilitate the rhythm and pattern of limb muscle activation. The basic genetic programs that govern connectivity between spinal interneurons and motor neurons are poorly understood due in large part to the complexity of the hundreds of muscle groups targeted by spinal locomotor circuits. In this exploratory proposal, we will assess the composition and connectivity of locomotor circuits in the little skate Leucoraja erinacea, a primitive cartilaginous fish that displays walking behaviors highly similar to those of tetrapods. Remarkably, we have found that the molecular profiles of fin-innervating motor neurons in Leucoraja are nearly identical to those of tetrapods. Leucoraja generates bipedal locomotion using 8 anatomically well-defined pelvic fin muscles, although the neural circuits that generate this behavior are uncharacterized. In this proposal we will determine the subtype identities and connectivity of spinal motor neurons, interneurons, and muscle in Leocoraja. We will also explore the utility of Leucoraja for assessing motor circuit connectivity programs using viral trans-synaptic tracing assays and electrophysiology. In Aim 1 we will assess the circuit composition and connectivity of motor neurons and interneurons in Leucoraja, and explore the role signaling through Hox transcription factors in the regional allocation of motor neuron columnar and pool subtype identities. In Aim2 we will use viral tracing assays to determine the pattern of connectivity between spinal interneurons and motor neurons, and explore the workings of the intraspinal central pattern generators (CPGs) that coordinate the activation of fin muscles during walking and swimming. By exploiting the relatively simple neuromusculature architecture of this primitive vertebrate, and building off our in depth knowledge of neural specification programs in the mammalian spinal cord, these studies could provide insights into the basic mechanisms through which motor circuits are assembled.