Consequences of Developmental Defects in Somatosensory Map formation

摘要 小鼠的胡须-桶系统是研究模式神经机制的常用神经生物学模型。 大脑的形成、依赖活动的连接精细化、经验和依赖使用的可塑性 神经发育和障碍的小鼠模型中的皮层回路、感觉和认知缺陷。一 使这一系统非常吸引人的特征之一是，鼻子上的胡须图案阵列是 由躯体感觉通路的几个层次的神经模型所代表。在过去几十年里， 大量的研究表明，感觉外周和内在的分子线索的重要性 丘脑和皮质在这个系统的图案中。我们一直在研究一种独特的突变小鼠模型， 在外周完整的情况下，丘脑和皮质的线索是完整的，但上升的躯体感觉通路是完整的。 脑干和丘脑之间的联系被破坏，导致双侧胡须图谱和图案的形成 丘脑和皮质。我们在当前资助期的研究揭示了几种形态和 这一小鼠品系的行为表型。 我们的继续学习将有三个目标： 1.完成小鼠丘脑和皮质通路的环路标测 脑干三叉神经丘脑轴突引导缺陷。我们问了以下问题：双面肌是如何 SI皮质中的MAP会影响S1-M1(初级运动皮质)和颧骨连接吗？ 2.确定S1下游区域“双面”反应的功能组织和后果 关于感性行为。我们将使用通道跨大脑皮层进行在体电生理记录 层状硅探头阵列。接下来，我们将在清醒的小鼠身上进行WM1的细胞分辨率钙成像 以映射双面映射的下游皮质后果。我们将测试Krox20cre/Robo3lox/lox小鼠 利用光遗传沉默的胡须辨别任务来探测大脑对双面图的使用。 3.确定该双界面体系的临界周期塑性的运行规律。我们提出以下要求 问：损伤反应中双侧皮质图的临界期可塑性有什么特点？ 还是感觉剥夺？单侧感觉剥夺是如何影响大脑皮层的每一幅图的？

Summary The whisker-barrel system of mice is a popular neurobiological model for studies of neural mechanisms of pattern formation in the brain, activity-dependent refinement of connections, experience and use-dependent plasticity of cortical circuits, and sensory and cognitive deficits in mouse models of neurodevelopmental and disorders. One of the features that makes this system very attractive is that the patterned array of whiskers on the snout is represented by neural models at several levels of the somatosensory pathway. Over the past several decades, numerous studies demonstrated the importance of the sensory periphery and the intrinsic molecular cues of the thalamus and cortex in patterning of this system. We have been working on a unique mutant mouse model, where the periphery is intact, thalamic and cortical cues are intact but the ascending somatosensory pathway between the brainstem and thalamus is disrupted, leading to bilateral whisker map and pattern formation in the thalamus and cortex. Our studies during the current funding period revealed several morphological and behavioral phenotypes in this mouse line. Our continuation studies will have three aims: 1. To complete circuit mapping along the thalamocortical and corticocortical pathways in mice with trigeminothalamic axon guidance defects in the brainstem. We ask the following questions: How does the bifacial map in the SI cortex affect S1-M1 (primary motor cortex) and callosal connections? 2. To determine functional organization of “bifacial” responses in areas downstream of S1, and consequences on perceptual behavior. We will record electrophysiologically in vivo across cortical layers using 64-channel laminar silicon probe arrays. We will next conduct cellular-resolution calcium imaging from wM1 in awake mice to map downstream cortical consequences of the bifacial map. We will test the Krox20cre/Robo3lox/lox mice for whisker discrimination tasks with optogenetic silencing to probe brain’s use of bifacial map. 3. To determine the operating rules of critical period plasticity in this bifacial system. We ask the following questions: What are the characteristics of critical period plasticity in bilateral cortical maps in response to injury or sensory deprivation? How does unilateral sensory deprivation affect each of the maps in the cortex?