The Role of Cell Lineage in Determining Tuning Preferences in Visual Cortex

细胞谱系在决定视觉皮层调节偏好中的作用

• 批准号: 8525975
• 负责人: Cathryn Rene Cadwell
• 金额: $ 3.88万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8525975
• 关键词: Address; Adult; Age; Area; Autistic Disorder; Brain; Calcium; Cell Lineage; Cells; Cerebral cortex; Cognition; Cognition Disorders; Complex; Development; Dose; Down Syndrome; Enhancers; Epigenetic Process; Eye; Foundations; Genetic; Image; Individual; Injection of therapeutic agent; Knowledge; Label; Lead; Light; Measures; Methods; Mus; Neocortex; Neurodevelopmental Disorder; Neurons; Neurophysiology - biologic function; Patients; Perception; Process; Property; Psyche structure; Publishing; Pyramidal Cells; Reporter; Reporting; Research; Research Personnel; Retroviridae; Role; Schizophrenia; Sister; Structure; Surface; System; Tamoxifen; Testing; Time; Ventricular; Visual; Visual Cortex; age effect; area striata; base; daughter cell; density; experience; hippocampal pyramidal neuron; in utero; in vivo; information processing; insight; juvenile animal; migration; neocortical; nerve stem cell; neurogenesis; novel; postnatal; preference; progenitor; public health relevance; research study; response; two-photon; visual stimulus

DESCRIPTION (provided by applicant): The cerebral cortex is perhaps the most complex structure in the brain, consisting of billions of neurons with trillions of connections. This high level of complexity underlies the massive computational power of the cortex and allows us to perceive the world around us and organize appropriate actions. In an effort to understand how the cortex as a whole functions neuroscientists have attempted to study smaller functional units within the cortex. It has been proposed that the smallest computational unit of the cortex may be the ontogenetic column - vertical columns of pyramidal neurons derived from a single neural progenitor cell. Recent studies suggest that cell lineage is an important predictor for development of functional properties in the neocortex. However, large differences in effect size between studies have led to controversy surround how important cell lineage is in determining function. This project will use in vivo two-photon calcium imaging to characterize visual response properties of clonally- related neurons in mouse primary visual cortex (V1). A tamoxifen-inducible Cre-loxP system will be used to sparsely label neural progenitor cells with a fluorescent marker at the beginning of neurogenesis. The dose and timing of tamoxifen administration will be optimized for spatial isolation of single microcolumns. Calcium responses of related and nearby unrelated neurons in V1 will be used to calculate orientation tuning for individual cells. We will systematically vary age at imaging and clonal size (two variables that have not been controlled for in previous studies) to determine whether these parameters contribute to the variability between studies. In addition, these experiments will lead important insights into the developmental time course of tuning properties of clonally related neurons. While the proposed studies will directly address the significance of ontogenetic microcolumns for encoding visual stimuli, the results will carry implications for the role of microcolumnar unit as a general principle of cortical processing. The proposed experiments may provide a circuit level foundation to study neurodevelopmental disorders such as autism and schizophrenia.

描述（由申请人提供）：大脑皮层可能是大脑中最复杂的结构，由数十亿个神经元和数万亿个连接组成。这种高度的复杂性是皮层强大计算能力的基础，使我们能够感知周围的世界并组织适当的行动。为了了解皮层作为一个整体如何发挥作用，神经科学家试图研究皮层内更小的功能单元。有人提出，皮层的最小计算单元可能是个体发生柱——源自单个神经祖细胞的锥体神经元的垂直柱。最近的研究表明，细胞谱系是新皮质功能特性发展的重要预测因子。然而，研究之间效应大小的巨大差异引发了围绕细胞谱系在决定功能方面的重要性的争议。该项目将使用体内双光子钙成像来表征小鼠初级视觉皮层（V1）中克隆相关神经元的视觉反应特性。他莫昔芬诱导型 Cre-loxP 系统将用于在神经发生开始时用荧光标记稀疏地标记神经祖细胞。他莫昔芬给药的剂量和时间将针对单个微柱的空间隔离进行优化。 V1 中相关和附近不相关神经元的钙反应将用于计算单个细胞的方向调整。我们将系统地改变成像年龄和克隆大小（之前的研究中未控制的两个变量），以确定这些参数是否会导致研究之间的差异。此外，这些实验将带来对克隆相关神经元调节特性的发育时间过程的重要见解。虽然拟议的研究将直接解决个体发育微柱对于编码视觉刺激的重要性，但结果将对微柱单元作为皮质处理的一般原理的作用产生影响。拟议的实验可能为研究自闭症和精神分裂症等神经发育障碍提供电路水平基础。