Consequences of Developmental Defects in Somatosensory Map formation

体感图形成发育缺陷的后果

• 批准号: 10579827
• 负责人: Reha S Erzurumlu
• 金额: $ 49.63万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579827
• 关键词: Adult; Affect; Area; Axon; Behavior; Bilateral; Brain; Brain Stem; Calcium; Cell Nucleus; Cells; Cerebral hemisphere; Characteristics; Cognitive deficits; Congenital Abnormality; Contralateral; Cues; DNA Sequence Alteration; Defect; Development; Disease; Electrophysiology (science); Face; Functional Magnetic Resonance Imaging; Funding; Genetic; Human Genetics; Image; Investigation; Longevity; Maps; Modeling; Molecular; Morphology; Motor; Motor Cortex; Mus; Mutant Strains Mice; Mutation; Neocortex; Neurobiology; Neurons; Nociception; Outcome; Pathway interactions; Pattern; Pattern Formation; Perception; Peripheral; Positioning Attribute; Process; Resolution; Rest; Rodent; Role; Sensory; Sensory Deprivation; Sensory Process; Side; Signal Transduction; Silicon; Sorting; Study models; System; Systems Development; Tactile; Testing; Thalamic structure; Tracer; Trigeminal System; Vibrissae; Visual; Weight; awake; axon guidance; barrel cortex; behavioral phenotyping; cortex mapping; critical developmental period; critical period; deprivation; experience; functional plasticity; in vivo; motor behavior; mouse model; mutant mouse model; neocortical; neonate; neural; neural model; neural patterning; neuromechanism; novel; optogenetics; response; response to injury; sensory input; sensory system; somatosensory; whisker discrimination

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?

总结 小鼠须-桶系统是研究模式神经机制的常用神经生物学模型 大脑中的形成，活动依赖的连接细化，经验和使用依赖的可塑性， 皮质回路，以及神经发育和障碍的小鼠模型中的感觉和认知缺陷。一 使这个系统非常吸引人的特征之一是，鼻子上的胡须图案阵列， 以躯体感觉通路的几个层次的神经模型为代表。在过去的几十年里， 许多研究表明，感觉外周和内在的分子线索的重要性， 丘脑和皮层在这个系统的模式。我们一直在研究一种独特的突变小鼠模型， 在外周神经完整的地方，丘脑和皮质的线索也是完整的，但上升的躯体感觉通路 脑干和丘脑之间的连接中断，导致双侧须状图和图案形成， 丘脑和皮质。我们在当前资助期间的研究揭示了几种形态学和 行为表型的变化 我们的继续学习将有三个目标： 1.为了完成小鼠丘脑皮质和皮质皮质通路的沿着回路映射， 脑干中的三叉神经丘脑轴突引导缺陷。我们提出以下问题： S1-M1（初级运动皮层）和胼胝体连接的影响？ 2.确定S1下游区域“双面”反应的功能组织及其后果 关于知觉行为。我们将在体内使用64通道记录跨皮层的电生理学 层状硅探针阵列。接下来，我们将在清醒小鼠中对wM 1进行细胞分辨率钙成像 来绘制双向映射的下游皮层结果。我们将测试Krox 20 cre/Robo 3lox/lox小鼠 胡须辨别任务与光遗传学沉默，以探测大脑的双面地图的使用。 3.确定该双面系统的临界期塑性的工作规律。我们提出以下要求 问题：损伤后双侧皮质映射的关键期可塑性特征是什么 还是感官剥夺单侧感觉剥夺是如何影响大脑皮层中的每一个地图的？