Mechanisms of receptive field establishment in mouse visual cortex

小鼠视觉皮层感受野建立机制

• 批准号: 8714870
• 负责人: JENNIFER Lyn HOY
• 金额: $ 5.33万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8714870
• 关键词: Address; Adult; Affect; Behavior; Biological; Cell physiology; Cells; Communities; Data; Data Analyses; Development; Developmental reading disorder; Disease; Electrophysiology (science); Exhibits; Eye; Foundations; Frequencies; Future; Genetic; Growth; Human; Knowledge; Lead; Life; Link; Long-Term Potentiation; Measures; Mediating; Mental Depression; Methods; Modeling; Molecular; Mus; Mutation; N-Methyl-D-Aspartate Receptors; Neurodevelopmental Disorder; Pathway interactions; Perception; Phase; Population; Process; Property; Receptor Signaling; Research; Research Training; Role; Schizophrenia; Sensory; Sensory Process; Shapes; Silicon; Staging; Synapses; Synaptic plasticity; Techniques; Testing; Thalamic structure; Time; Training; Vision; Visual; Visual Cortex; Visual Perception; Visual system structure; Work; area striata; awake; base; brain shape; cell type; density; experience; extracellular; in vivo; insight; novel; orientation selectivity; programs; public health relevance; receptive field; receptor function; response; stem; synaptogenesis; vision development; visual process; visual processing; visual receptive field; visual stimulus

DESCRIPTION (provided by applicant): Vision dominates the human sensory experience, and the visual cortex in particular is critical for understanding the world around us. During development, molecular and cellular processes such as synapse formation and refinement shape the circuitry underlying the appropriate function of the visual cortex. Therefore, a clear understanding of the mechanisms that support visual system development would facilitate our ability to address neurodevelopmental disorders that impair visual perception. The work proposed herein will provide an important link between the molecular mechanisms of synaptic development and the emergence of specific functional response properties in the primary visual cortex of the awake mouse. In specific aim 1, I will determine the time-course for the emergence and refinement of several basic receptive field (RF) properties in mouse visual cortex from eye opening to the adult. I will measure extracellular unit activity with high-density silicon probes that span several layers of cortex, while optimized visual stimuli are presented to the mouse. From these recordings, I will use recently developed data analysis techniques to quantify the receptive field properties of distinct classes of cells - excitatory, inhibitory, and specific layers - as they evolve over development. Specifically, I will delineate the ontogeny of orientation selectivity (OS), spatial frequency tuning (SF) and response linearity across these distinct cell types. This will constitute the first complete characterization of the development of these RF properties in the awake mouse visual cortex employing electrophysiology; and it will yield novel cell type and layer specific information that will be required for future mechanistic studies by our lab and others. In specific aim 2, I will delete specific N-methyl-D-Aspartate receptor (NMDAR) subunits, NR2B or NR2A, from a targeted class of cells where OS first arises in the visual system. Differential expression of these subunits relate to specific developmental phases of visual system development. Therefore, I will test the hypothesis that NR2B and NR2A differentially underlie the establishment and subsequent refinement, respectively, of several RF properties in visual cortex (V1). I will specifically measure the RF properties outlined above at key time-points in development in mice where NR2B or NR2A has been deleted from a specific excitatory cell population that densely occupies layer IV of visual cortex. This integrative approach will significantly impact our understanding of the mechanisms that underlie the development of function in the visual system. Specifically, our targeted studies will add unprecedented mechanistic knowledge of where and when NMDAR mediated activity is required for the establishment and refinement of V1 response properties over early development.

描述（由申请人提供）：视觉主导着人类的感觉体验，尤其是视觉皮层对于理解我们周围的世界至关重要。在开发过程中，分子和细胞过程（例如突触形成和精致）塑造了视觉皮层适当功能的基础电路。因此，对支持视觉系统发展的机制有清晰的了解将有助于我们解决损害视觉感知的神经发育障碍的能力。本文提出的工作将提供突触发育的分子机制与醒着小鼠的主要视觉皮层中特定功能响应特性的出现之间的重要联系。 在特定的目标1中，我将确定从眼睛开放到成人的小鼠视觉皮层中几种基本接受场（RF）特性的出现和完善的时间。我将用高密度的硅探针测量细胞外单位活性，这些硅探针跨越了几层皮层，同时将优化的视觉刺激呈现给小鼠。从这些记录中，我将使用最近开发的数据分析技术来量化不同类别的细胞（兴奋性，抑制性和特定层）的接收场特性，它们会随着发育而发展。具体而言，我将描述这些不同细胞类型的方向选择性（OS），空间频率调整（SF）和响应线性的个体发育。这将构成对发展的第一个完整表征 这些RF特性在醒着的小鼠视觉皮层中采用电生理学；它将产生新型的细胞类型和层特定的信息，这将是我们实验室和其他人将来的机械研究所需的。 在特定的目标2中，我将从视觉系统中首先出现OS的靶向细胞类别中删除特定的N-甲基-D-天冬氨酸受体（NMDAR）亚基NR2B或NR2A。这些亚基的差异表达与视觉系统发展的特定发育阶段有关。因此，我将检验以下假设：NR2B和NR2A分别在视觉皮层（V1）中分别对几种RF特性的建立和随后的完善基础。我将在小鼠的开发中特定测量上面概述的RF性能，其中NR2B或NR2A已从特定的兴奋性细胞种群中删除，该细胞群密度占据了视觉皮层的IV层。 这种综合方法将极大地影响我们对视觉系统功能发展的机制的理解。具体而言，我们的目标研究将增加前所未有的机械知识，以了解NMDAR介导的活动在早期开发过程中建立和完善V1响应特性所需的何时何地。