Semi-Natural Rearing Conditions Alter the Trajectory of Sensorimotor Cortical Development: Functional Connectivity and Behavior

半自然饲养条件改变感觉运动皮层发育的轨迹：功能连接和行为

• 批准号: 9908718
• 负责人: Mackenzie Englund
• 金额: $ 3.74万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-03 至 2023-01-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908718
• 关键词: ARHGEF5 gene; Adaptive Behaviors; Address; Adult; Age; Anatomy; Animals; Area; Behavior; Behavioral; Behavioral Assay; Bilateral; Body part; Brain; Complex; Computer software; Contralateral; Development; Dimensions; Environment; Forelimb; Gait; Goals; Growth; Hindlimb; Histologic; Injections; Ipsilateral; Laboratories; Laboratory Animals; Laboratory Rat; Lead; Life; Maps; Modification; Motor; Motor Cortex; Motor output; Movement; Neocortex; Organism; Parietal Lobe; Pattern; Performance; Phenotype; Rat-1; Rattus; Reflex action; Reproduction; Sensory; Sensory Deprivation; Specific qualifier value; Structure; Surface; System; Tail; Techniques; Testing; Time; Variant; Vibrissae; Walking; anatomical tracing; behavior test; density; early experience; experimental study; grasp; microstimulation; postnatal; relating to nervous system; sensory input; success; young adult

The developing neocortex is highly malleable. Early experience tunes neural systems to match an organism’s environmental context, allowing the organism to generate adaptive behavior necessary for survival, growth, and reproduction in a changing environment. For decades, paradigms of sensory deprivation and enrichment have been used to show how early sensory input dramatically alters the connectivity and functional organization of primary sensory areas in the neocortex. How these changes in sensory input lead to changes in motor output, and how the developmental trajectory is altered to produce these changes, is unknown. Further, there are few studies that examine how differences in motor opportunities (affordances), particularly those available in large three-dimensional spaces, impact the motor system. We address this issue by rearing rats in a dynamic semi-natural environment 3000 times the size of standard laboratory cages, and quantifying changes in the connectivity and functional organization of motor cortex, and subsequent behavior, at different developmental milestones. In the current proposal, we seek to elucidate what and when specific modifications are made to motor cortex due to variations in the early postnatal environment. We will do this by comparing the emergence of sensorimotor behaviors between laboratory and semi-naturally reared rats, quantifying differences in when behavioral milestones are reached, how well animals accomplish sensorimotor tasks, and what strategies they use to do so. Following behavioral assays, we will examine differences in the intrinsic connectivity (microcircuitry) and organization of primary motor cortex (M1), assessing the distribution and density of connections between movement representations within M1. Additionally, we will examine the emergence of movement representations of different body parts within M1 at different developmental time points using intracortical microstimulation techniques. Finally, we will quantify differences in the macrocircuitry of M1, examining connectivity with other cortical fields within and across hemispheres as well as with subcortical structures. This is the first study that rears laboratory animals in a large and dynamic wild-type environment to systematically address how early experience impacts the development of motor areas of the cortex and the coordinated behaviors that the brain generates.

发展中的新皮层具有很高的延展性。早期体验调谐神经系统以匹配生物的 环境环境，使生物体能够产生生存，生长，生长所必需的自适应行为 和在不断变化的环境中繁殖。几十年来，感觉剥夺和富集的范式 已被用来显示早期感觉输入如何显着改变连接性和功能性 新皮层中的主要感觉区域的组织。感觉输入中的这些变化如何导致变化 在电动机输出以及如何改变发育轨迹以产生这些变化的情况下，未知。 此外，很少有研究研究汽车机会（负担能力）的差异如何，尤其是 在大型三维空间中可用的人会影响电动机系统。我们通过饲养解决这个问题 动态半自然环境中的大鼠是标准实验室笼的大小的3000倍，并量化 运动皮层的连通性和功能组织的变化，以及随后的行为，在不同 发展里程碑。在当前的建议中，我们试图阐明什么以及何时进行特定修改 我们将通过比较 实验室和半自然饲养大鼠之间的感觉运动行为的出现，量化 达到行为里程碑时的差异，动物完成的感觉运动任务的能力以及 他们用什么策略来做到这一点。以下行为分析，我们将检查内在的差异 连通性（微电路）和原发性运动皮层（M1）的组织，评估分布和 M1内运动表示之间的连接密度。此外，我们将研究 M1在不同发育时间内不同身体部位运动表示的出现 使用皮质内微刺激技术的点。最后，我们将量化大环路的差异 M1，检查与半球内外其他皮质场的连通性以及 皮层结构。这是第一项在大型且动态的野生型中培养实验动物的研究 有系统地解决早期经验如何影响运动区域发展的环境 大脑产生的皮层和协调行为。