Consequences of Developmental Defects in Somatosensory Map formation

体感图形成发育缺陷的后果

• 批准号: 10362741
• 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/10362741
• 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; 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; Neurodevelopmental Disorder; 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; Study models; System; Systems Development; Tactile; Testing; Thalamic structure; Tracer; Trigeminal System; Vibrissae; Visual; Weight; awake; axon guidance; barrel cortex; base; behavioral phenotyping; cortex mapping; critical developmental period; critical period; deprivation; experience; functional plasticity; in vivo; motor behavior; mouse model; mutant mouse model; neonate; neural model; neural patterning; neuromechanism; novel; optogenetics; relating to nervous system; 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?

概括 小鼠的胡须桶系统是一种流行的神经生物学模型，用于研究模式的神经机制 大脑的形成、连接的活动依赖的细化、经验和使用依赖的可塑性 神经发育和疾病小鼠模型中的皮质回路以及感觉和认知缺陷。一 使该系统非常有吸引力的特征之一是鼻子上的胡须图案阵列 由体感通路多个层面的神经模型代表。在过去的几十年里， 大量研究证明了感觉外围和内在分子线索的重要性 丘脑和皮质参与该系统的模式化。我们一直在研究一种独特的突变小鼠模型， 在外围完好的情况下，丘脑和皮质线索完好无损，但上行体感通路 脑干和丘脑之间的神经元被破坏，导致双侧胡须图和模式形成 丘脑和皮质。我们在当前资助期间的研究揭示了一些形态和 该小鼠品系的行为表型。 我们的继续学习将有三个目标： 1. 完成小鼠丘脑皮质和皮质皮质通路的电路图谱 脑干中的三叉丘脑轴突引导缺陷。我们提出以下问题： 双面 SI 皮层中的地图会影响 S1-M1（初级运动皮层）和胼胝体连接吗？ 2. 确定 S1 下游区域“双面”响应的功能组织及其后果 关于知觉行为。我们将使用 64 通道记录体内皮质层的电生理学 层状硅探针阵列。接下来我们将在清醒的小鼠中进行 wM1 的细胞分辨率钙成像 绘制双面图的下游皮质后果。我们将测试 Krox20cre/Robo3lox/lox 小鼠 胡须辨别任务与光遗传学沉默来探测大脑对双面图的使用。 3.确定该双面系统临界期塑性的运行规则。我们询问以下问题 问题：双侧皮质图响应损伤的关键期可塑性有哪些特征 还是感觉剥夺？单侧感觉剥夺如何影响皮质中的每个图？