Brainstem and spinal mechanisms of gait transition in a limbed vertebrate

有肢脊椎动物步态转变的脑干和脊柱机制

• 批准号: RGPIN-2017-05522
• 负责人: Ryczko, Dimitri
• 金额: $ 2.7万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=762072
• 关键词: Brainstem; spinal; mechanisms; gait; transition

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.

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）在运动控制中起重要作用。MLR刺激启动运动，刺激强度增加会增加运动速度并引起步态转变。MLR投射到激活脊髓运动网络的网状脊髓细胞。我们对这种回路的大部分了解都是从一种叫做七鳃鳗的鱼身上获得的。然而，在有肢脊椎动物中，这种电路如何控制步态转变尚不清楚。我的长期目标是利用电生理学、钙成像、神经解剖学和蝾螈运动分析等综合方法，确定脑干和脊髓细胞在步态转变中的作用。这些四足动物是研究步态转变背后的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，大脑暴露在外，身体自由活动，低MLR刺激强度唤起行走，而高强度唤起游泳。我未来5年的研究计划包括2个具体项目：1)MLR细胞在步行和游泳时激活网状脊髓核的机制。我们将使用示踪和免疫荧光来识别MLR到网状脊髓核的投影。连接将通过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在半完整的准备中停用向网状脊髓核的MLR输入来确定。一个博士生将负责这个项目。2)网状脊髓细胞控制轴向和肢体脊髓回路的机制。我们将使用示踪和免疫荧光识别网状脊髓投射到轴和肢脊髓细胞。利用电生理和钙显像技术记录脊髓网状刺激引起的轴向和肢体运动神经元的反应。我们将确定增加MLR刺激时是否会招募不同的脊髓细胞。两名硕士生将参与该项目。本科生将参与这两个项目。这一新发现将为脑干细胞及其脊柱靶点在四足动物步态转变中的作用提供更全面的视角。它将与A.J. Ijspeert博士（École Polytechnique FÉdÉrale de Lausanne）合作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的培训框架，为基础研究或应用于临床或生物工程领域的研究准备高素质的人才。