Brainstem and spinal mechanisms of gait transition in a limbed vertebrate

运动控制的一个显著特点是能够在运动模式(行走、游泳、飞行)之间切换。在脊椎动物中，中脑运动区(MLR)在运动控制中起着重要作用。MLR刺激可启动运动，增加刺激强度可提高运动速度并引发步态转换。MLR投射到激活脊髓运动网络的网状脊髓细胞。我们所知道的关于这个电路的大部分是从一种鱼--七鳗鱼那里获得的。然而，在有肢体的脊椎动物中，这种回路是如何控制步态转换的尚不清楚。*我的长期目标是利用包括电生理学、钙成像、神经解剖学和火蜥蜴运动分析在内的多种方法，确定脑干和脊髓细胞在步态转换中的作用。这些四足动物是研究步态转换潜在神经机制的理想选择，因为它们在水下游泳和在地面行走。在半完整的准备中，大脑暴露，身体可以自由移动，低MLR刺激强度让人联想到行走，而高强度刺激让人联想到游泳。*我未来5年的研究计划包括两个具体项目：*1)MLR细胞在行走和游泳过程中激活网状脊髓核的机制。我们将使用示踪和免疫荧光来确定MLR投射到网状脊髓核。连接性将通过使用电生理学和钙成像记录网状脊髓细胞中MLR诱发的反应来验证。这种连通性的行为作用将通过停用半完整制剂中对网状脊髓核的MLR输入来确定。一名博士生将负责这一项目。*2)网状脊髓细胞控制轴向和肢体脊髓回路的机制。我们将使用示踪法和免疫荧光法确定网状脊髓向轴向和肢体脊髓细胞的投射。用电生理学和钙成像技术记录刺激网状脊髓在轴向和肢体运动神经元中所引起的反应。我们将确定在增加MLR刺激时是否招募了不同的脊髓细胞。两名硕士研究生将参与这个项目。本科生将为这两个项目做出贡献。*这一新知识将提供一个更全面的视角，了解脑干细胞及其脊髓靶标在四足动物步态转变中的作用。它将用于开发创新的脑机接口，与公关合作控制运动设备。A.J.伊斯皮尔特(洛桑联邦理工学院)。我的研究方法将提供一个综合培训框架，为基础研究或应用于临床或生物工程领域的研究领域的职业生涯培养高素质的人才。

A striking feature of locomotor control is the ability to switch between locomotor modes (walking, swimming, flying). In vertebrates, the Mesencephalic Locomotor Region (MLR) plays an important role in locomotor control. MLR stimulation initiates locomotion and increasing stimulation intensity increases locomotor speed and elicits gait transitions. The MLR projects to reticulospinal cells that activate the spinal locomotor networks. Much of what we know about this circuitry was obtained in a fish, the lamprey. However, in limbed vertebrates, how this circuitry controls gait transitions is unknown. ******My long-term goal is to identify the role of brainstem and spinal cells in gait transition using a combination of approaches including electrophysiology, calcium imaging, neuroanatomy and movement analysis in salamanders. These tetrapods are ideal to study the neural mechanisms underlying gait transition, as they swim underwater and walk on ground. In semi-intact preparations where the brain is exposed and the body is free to move, low MLR stimulation intensities evoke walking, whereas higher intensities evoke swimming. ***My research program for the next 5 years contains 2 specific projects: ***1) Mechanisms through which MLR cells activate reticulospinal nuclei during walking and swimming. We will identify MLR projections to reticulospinal nuclei using tracing and immunofluorescence. Connectivity will be validated by recording MLR-evoked responses in reticulospinal cells using electrophysiology and calcium imaging. The behavioural role of this connectivity will be identified by deactivating MLR inputs to reticulospinal nuclei in semi-intact preparations. A Ph.D. student will be in charge of this project.***2) Mechanisms through which reticulospinal cells control axial and limb spinal circuits. We will identify the reticulospinal projections to axial and limb spinal cells using tracing and immunofluorescence. The responses evoked by reticulospinal stimulation in axial and limb motoneurons will be recorded using electrophysiology and calcium imaging. We will determine whether different spinal cells are recruited when increasing MLR stimulation. Two master's students will be involved in the project. Undergraduate students will contribute to both projects. ******The new knowledge will provide a more comprehensive view of the role of brainstem cells and their spinal targets in gait transition in tetrapods. It will serve for developing innovative brain-machine interfaces to control locomotor devices in collaboration with Pr. A.J. Ijspeert (École Polytechnique Fédérale de Lausanne). My research approach will provide an integrated training framework preparing highly qualified personnel for careers in basic research or research applied to clinical or bioengineering fields.