PDF(Pubmed)
Abstract：
The limited information about how descending inputs from the brain and sensory inputs from the periphery use spinal cord interneurons (INs) is a major barrier to understanding how these inputs may contribute to motor functions under normal and pathologic conditions. Commissural interneurons (CINs) are a heterogeneous population of spinal INs that has been implicated in crossed motor responses and bilateral motor coordination (ability to use the right and left side of the body in a coordinated manner) and, therefore, are likely involved in many types of movement (e.g., dynamic posture stabilization, jumping, kicking, walking). In this study, we incorporate mouse genetics, anatomy, electrophysiology, and single-cell calcium imaging to investigate how a subset of CINs, those with descending axons called dCINs, are recruited by descending reticulospinal and segmental sensory signals independently and in combination. We focus on two groups of dCINs set apart by their principal neurotransmitter (glutamate and GABA) and identified as VGluT2+ dCINs and GAD2+ dCINs. We show that VGluT2+ and GAD2+ dCINs are both extensively recruited by reticulospinal and sensory input alone but that VGluT2+ and GAD2+ dCINs integrate these inputs differently. Critically, we find that when recruitment depends on the combined action of reticulospinal and sensory inputs (subthreshold inputs), VGluT2+ dCINs, but not GAD2+ dCINs, are recruited. This difference in the integrative capacity of VGluT2+ and GAD2+ dCINs represents a circuit mechanism that the reticulospinal and segmental sensory systems may avail themselves of to regulate motor behaviors both normally and after injury.SIGNIFICANCE STATEMENT The way supraspinal and peripheral sensory inputs use spinal cord interneurons is fundamental to defining how motor functions are supported both in health and disease. This study, which focuses on dCINs, a heterogeneous population of spinal interneurons critical for crossed motor responses and bilateral motor coordination, shows that both glutamatergic (excitatory) and GABAergic (inhibitory) dCINs can be recruited by supraspinal (reticulospinal) or peripheral sensory inputs. Additionally, the study demonstrates that in conditions where the recruitment of dCINs depends on the combined action of reticulospinal and sensory inputs, only excitatory dCINs are recruited. The study uncovers a circuit mechanism that the reticulospinal and segmental sensory systems may avail themselves of to regulate motor behaviors both normally and after injury.
摘要：
关于来自大脑的下降输入和来自外围的感觉输入如何利用脊髓中间神经元（IN）的有限信息是理解这些输入如何在正常和病理条件下有助于运动功能的主要障碍。委托中间神经元（CIN）是脊髓INs的异质群体，涉及交叉运动反应和双侧运动协调（以协调方式使用身体右侧和左侧的能力），因此,可能涉及许多类型的运动(例如，动态姿态稳定,跳跃,踢,步行)。在这项研究中,我们结合了老鼠遗传学，解剖学,电生理学,和单细胞钙成像来研究CINs的子集，那些有下降轴突（dCIN），通过独立地和组合地降低网状脊髓和节段感觉信号来招募。我们专注于由其主要神经递质（谷氨酸和GABA）分开的两组dCIN，并鉴定为VGLUT2dCIN和GAD2dCIN。我们表明，VGLUT2和GAD2dCIN均仅通过网状脊髓和感觉输入广泛招募，但VGLUT2和GAD2dCIN对这些输入的整合方式不同。严重的,我们发现，当募集取决于网状脊髓和感觉输入(亚阈值输入)的联合作用时，VGLUT2+dCIN,但不是GAD2+dCIN，被招募。VGLUT2和GAD2dCIN的整合能力的这种差异代表了一种回路机制，即网状脊髓和节段感觉系统可以利用自己来调节正常和受伤后的运动行为。意义陈述脊柱上和外周感觉输入利用脊髓中间神经元的方式是定义运动功能在健康和疾病中如何得到支持的基础。这项研究,专注于下降的连合中间神经元(dCIN)，对交叉运动反应和双侧运动协调至关重要的脊髓中间神经元的异质群体，显示谷氨酸能（兴奋性）和GABA能（抑制性）dCIN均可通过脊柱上（网状脊髓）或外周感觉输入募集。此外,研究表明，在dCIN的募集取决于网状脊髓和感觉输入的联合作用的条件下，只招募兴奋性dCIN。该研究揭示了一种回路机制，网状脊髓和节段性感觉系统可能会在正常和受伤后调节运动行为。
