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?

概括 小鼠的晶须桶系统是一种用于研究模式神经力学的流行神经生物学模型 大脑中的形成，连接，经验和使用依赖性可塑性的依赖于活动的改进 神经发育和疾病的小鼠模型中的皮质回路以及感觉和认知缺陷。一 使该系统非常吸引人的功能是，鼻子上的图案阵列是 在体感途径的几个级别上以神经元模型为代表。在过去的几十年中， 大量研究表明，感觉外周和固有分子提示的重要性 丘脑和皮质在该系统的图案中。我们一直在研究独特的突变鼠标模型， 外围完整的地方，丘脑和皮质提示是完整的，但升高的体感途径 在脑干和丘脑之间被破坏，导致双侧晶须图和图案形成 丘脑和皮质。我们在当前资金期间的研究表明了几种形态学和 该鼠标线中的行为表型。 我们的继续研究将有三个目标： 1。沿着丘脑皮质和皮质皮质途径完成小鼠的电路映射 脑干中的三角形丘脑轴突引导缺陷。我们提出以下问题：双面 Si Cortex中的地图会影响S1-M1（主电机皮层）和Callosal连接？ 2。确定S1下游区域中“双面”响应的功能组织以及后果 关于感知行为。我们将使用64通道在整个皮质层的体内进行电生理记录 层状硅探针阵列。接下来，我们将在清醒小鼠中从WM1进行细胞分辨率钙像成像 绘制双面图的下游皮质后果。我们将测试KROX20CRE/ROBO3LOX/LOX小鼠的 晶须歧视任务具有光遗传沉默，以探测大脑对双面图的使用。 3。确定该双面系统中关键时期可塑性的操作规则。我们问以下 问题：双侧皮质图中关键时期可塑性的特征是什么 还是感觉剥夺？单方面感觉剥夺如何影响皮质中的每个地图？