Longitudinal structure of spinal premotor circuits

脊髓前运动回路的纵向结构

• 批准号: 10577360
• 负责人: Martha W Bagnall
• 金额: $ 39.08万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-15 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10577360
• 关键词: Ablation; Animals; Anterior Horn Cells; Axon; Behavioral; Biological; Biological Assay; Charge; Clinical; Computer Models; Contralateral; Data; Ensure; Exhibits; GATA3 gene; Head; Home; Horns; Injury; Ipsilateral; Leg; Locomotion; Logic; Mammals; Maps; Measures; Modeling; Morphology; Motor; Motor Neurons; Movement; Muscle Contraction; Natural regeneration; Neurons; Organism; Output; Pattern; Physiological; Population; Positioning Attribute; Publishing; Sensory; Slice; Spinal; Spinal Cord; Stimulus; Structure; Synapses; Synaptic Potentials; Tail; Target Populations; Testing; Translating; V1 neuron; Vertebral column; Walking; Whole-Cell Recordings; Work; Zebrafish; arm; dorsal horn; experimental study; in vivo; inhibitory neuron; optogenetics; postsynaptic; predictive modeling; spinal cord repair; spine bone structure

Project Summary As animals locomote, they constantly coordinate activity between the rostral and caudal ends of the body. This coordination relies on neurons in the spinal cord that send long ascending or descending axonal projections. Although several studies have shown that ablation of these neurons leads to deficits in coordination, it is largely unknown whether these long-range circuits are similar or different from local circuits. In recently published data in larval zebrafish, we demonstrated that at least one genetically defined class of spinal neurons, the V1 (En1+) population, changes its synaptic targets as its axon ascends in the spinal cord. Specifically, V1 neurons form synaptic connections with motor neurons and other ventral horn neurons nearby, but switch to inhibiting a dorsal horn sensory population at longer range. Here we propose to extend this analysis to five additional sets of ventral horn neurons, the dI6, V0 excitatory and inhibitory, V2a, and V2b populations. To create this large-scale circuit map, we use localized optogenetic activation of identified spinal populations while carrying out whole-cell recording of identified potential postsynaptic partners. By translating the optogenetic stimuli up and down the spinal cord, we can build a physiological map of the strength of the synaptic connection at various rostrocaudal positions. Normalization of the synaptic charge transfer allows comparisons across target populations, providing a comprehensive grid of connectivity among spinal neuron classes at various rostrocaudal distances. We will then build a computational model of spinal cord connectivity that reflects biological reality, as measured in these experiments. Using this model, we will test the consequences of shifting synaptic connections in the rostrocaudal axis, in order to understand the logic of spinal circuit organization. Finally, we will selectively ablate long-range or local V2a neurons to determine the behavioral effects of long-range vs local projections. Together, these experiments will provide a circuit map of genetically identified spinal neurons.

项目摘要 随着动物的发光，它们不断地协调身体的尾部和尾端之间的活性。这 协调依赖于脊髓中的神经元，这些神经元会发送长期上升或降轴突投影。 尽管几项研究表明，这些神经元的消融导致协调不足，但这是 这些远程电路在很大程度上尚不清楚与本地电路相似还是不同。在最近 在幼虫斑马鱼中发布的数据，我们证明了至少一类脊柱类别 神经元V1（EN1+）种群，随着其轴突升高在脊髓中，其突触靶变化。 具体而言，V1神经元与附近的运动神经元和其他腹角神经元形成突触连接， 但是，转而抑制更长范围内的背角感官人群。在这里，我们建议扩展这一点 分析五组腹角神经元，即DI6，V0兴奋性和抑制性，V2A和V2B 人群。为了创建这个大型电路图，我们使用已识别的脊柱的局部光遗传学激活 人口在进行确定的突触后伴侣的全细胞记录时。通过翻译 脊髓上下的光遗传刺激，我们可以建立一个生理图 在各种罗伯多德位置处的突触连接。突触电荷转移的归一化允许 比较目标人群，提供了脊柱神经元之间连通性的全面网格 在各种距离上的课程。然后，我们将建立脊髓连接的计算模型 如在这些实验中所测量的那样，这反映了生物学现实。使用此模型，我们将测试 为了理解逻辑 脊柱电路组织。最后，我们将有选择地烧毁远程或局部V2A神经元，以确定 远程与本地预测的行为影响。这些实验将共同提供一个电路图 遗传鉴定的脊柱神经元。