Brainstem and spinal mechanisms of gait transition in a limbed vertebrate

运动控制的一个显著特征是能够在运动模式（步行、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刺激启动运动，并且增加刺激强度增加运动速度和electrical步态转变。MLR投射到网状脊髓细胞，激活脊髓运动网络。我们对这种电路的了解，大部分是从一种鱼--七鳃鳗身上获得的。然而，在四肢脊椎动物中，这种电路如何控制步态过渡尚不清楚。我的长期目标是确定脑干和脊髓细胞在步态转换中的作用，使用包括电生理学，钙成像，神经解剖学和运动分析在内的方法相结合。这些四足动物非常适合研究步态转变背后的神经机制，因为它们在水下游泳并在地面上行走。在大脑暴露且身体自由移动的半完整制剂中，低MLR刺激强度引起行走，而较高强度引起游泳。我未来5年的研究计划包括2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。我们将确定MLR预测网状脊髓核使用跟踪和免疫荧光。将通过使用电生理学和钙成像记录网状脊髓细胞中的MLR诱发反应来验证连接性。这种连接的行为作用将通过在半完整的制剂中使MLR输入到网状脊髓核失活来确定。博士学位学生将负责这个项目。2）网状脊髓细胞控制轴向和肢体脊髓回路的机制。我们将使用追踪和免疫荧光来识别网状脊髓向轴向和肢体脊髓细胞的投射。将使用电生理学和钙成像记录网状脊髓刺激在轴向和肢体运动神经元中诱发的反应。我们将确定当增加MLR刺激时是否招募不同的脊髓细胞。两名硕士生将参与该项目。本科生将为这两个项目做出贡献。新的知识将提供一个更全面的观点，脑干细胞和它们的脊髓目标在四足动物步态转换的作用。它将与A. J. Ijspeert教授（洛桑联邦理工学院）合作，用于开发创新的脑机接口，以控制运动设备。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提供高素质的人才。

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.