Feature Selectivity and Interneuron Connectivity Principles of Clonally-Related Excitatory Neurons in Mouse Primary Visual Cortex

小鼠初级视觉皮层克隆相关兴奋性神经元的特征选择性和中间神经元连接原理

• 批准号: 9545066
• 负责人: Paul Gerrard Fahey
• 金额: $ 4.66万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-20 至 2019-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9545066
• 关键词: Address; Adult; Autistic Disorder; Brain; Calcium; Cells; Cognition; Complex; Cortical Column; Development; Dimensions; Electrophysiology (science); Exhibits; Frequencies; Hippocampus (Brain); Image; Income; Individual; Interneurons; Location; Maintenance; Measures; Morphology; Mus; Neocortex; Neurons; Output; Pattern; Perception; Photons; Play; Process; Property; Recording of previous events; Research; Role; Schizophrenia; Sensory; Surface; Synapses; System; Testing; Visual; Visual Cortex; Work; area striata; brain abnormalities; brain research; excitatory neuron; experimental study; hippocampal pyramidal neuron; improved; in vivo calcium imaging; inhibitory neuron; insight; multi-photon; neocortical; neuropsychiatry; novel; receptive field; sensory input; synaptogenesis

7. PROJECT SUMMARY/ABSTRACT Perception, cognition, and other high level brain functions are thought to arise in the neocortex, a laminar sheet of neurons forming the surface of the brain. However, the billions of neurons and trillions of synaptic connections in the cortex form an overwhelmingly complex system, and therefore more insight into the organization of the cortex at the local circuit level is needed. Previous research has suggested that ontogenetic columns (columns of clonally-related neurons) play a critical role in excitatory neuron integration in local microcircuitry, and may represent a fundamental module of cortical computation. However, the functional relationships within an ontogenetic column and the principles of ontogenetic column integration into the local circuit of inhibitory interneurons have not been examined. This project will use multi-photon in vivo calcium imaging to characterize the visual feature selectivity of clonally-related neurons across all layers of primary visual cortex, and examine the distribution of feature selectivity within a layer, and how that distribution changes between cortical layers. Additionally, using octuple simultaneous whole cell patching, this project will test different classes of cortical inhibitory interneurons for patterns of connectivity to ontogenetic columns, in order to gain insight into how clonally related neurons integrate with unrelated neurons in the local circuit. Together, these experiments will delineate the influence of ontogenetic history on the functional organization and microcircuitry of adult neocortex. The results of this work have the potential to reveal fundamental new insights into how the brain processes incoming sensory information, and how that information is transformed as it passes from one cortical layer to another. These results will thus enable a more principled understanding of normal and abnormal circuit function, with broad implications for a wide range of currently intractable neuropsychiatric illnesses such as autism and schizophrenia.

7.项目总结/摘要 知觉、认知和其他高级大脑功能被认为是在新皮层中产生的， 形成大脑表面的一层神经元。然而，数十亿的神经元和数万亿的 皮层中的突触连接形成了一个极其复杂的系统，因此更深入地了解 需要在局部回路水平上组织皮层。先前的研究表明， 个体发育柱（克隆相关神经元柱）在兴奋性神经元整合中起关键作用 在局部微电路中，并且可能代表皮层计算的基本模块。但 个体发生柱内的功能关系和个体发生柱整合的原则 进入抑制性中间神经元的局部回路还没有被研究过。 本计画将使用多光子活体钙离子成像来表征视觉特徴的选择性 的克隆相关神经元在初级视觉皮层的所有层，并检查特征的分布 层内的选择性，以及皮层层之间的分布如何变化。此外，使用 八倍同时全细胞修补，该项目将测试不同类别的皮质抑制 interneurons的连接模式，以个体发育柱，为了深入了解如何克隆 相关神经元与局部回路中的不相关神经元整合。这些实验将 描述个体发育史对成年人功能组织和微电路的影响 新皮层这项工作的结果有可能揭示大脑是如何 处理传入的感官信息，以及这些信息在从一个 皮层到另一层因此，这些结果将使人们能够更有原则地理解正常和 回路功能异常，对目前难治性神经精神疾病的广泛影响 自闭症和精神分裂症等疾病。