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

发育中的新皮质具有很强的延展性。早期的经验调整神经系统以匹配有机体的 环境背景，允许有机体产生生存、生长、 以及在不断变化的环境中繁殖。几十年来，感官剥夺和丰富的范例 已经被用来展示早期的感觉输入如何戏剧性地改变连接和功能 大脑皮层初级感觉区的组织。感官输入的这些变化如何导致变化 运动输出的变化，以及发育轨迹是如何改变以产生这些变化的，目前尚不清楚。 此外，很少有研究研究运动机会(支付能力)的差异，特别是 那些在大的三维空间中可用的东西会影响电机系统。我们通过养育孩子来解决这个问题 在动态的半自然环境中，大鼠的尺寸是标准实验室笼子的3000倍，并量化 不同年龄组运动皮质的连通性和功能组织以及后续行为的变化 发展里程碑。在目前的提案中，我们试图澄清具体修改的内容和时间 由于出生后早期环境的变化，运动皮质受到影响。我们将通过比较 实验室和半自然饲养的大鼠之间感觉运动行为的出现，量化 在何时达到行为里程碑，动物在完成感觉运动任务方面的差异，以及 他们使用了什么策略来做到这一点。在行为分析之后，我们将检查内在的差异 初级运动皮质(M1)的连通性(微电路)和组织，评估分布和 M1内移动表示之间的连接密度。此外，我们还将研究 不同发育时期M1内不同部位运动表征的出现 使用皮质内微刺激技术的穴位。最后，我们将量化宏电路中的差异 ，检查与半球内和大脑半球之间的其他皮质区域的连通性，以及与 皮质下结构。这是第一次在大型、有活力的野生动物中饲养实验动物的研究 环境，系统地解决早期经验如何影响儿童运动区的发展 大脑皮层和大脑产生的协调行为。

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.