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: 8826582
• 负责人: JENNIFER Lyn HOY
• 金额: $ 5.6万
• 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/8826582
• 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; Health; 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; differential expression; experience; extracellular; in vivo; insight; novel; orientation selectivity; programs; 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官体验，视觉皮层对于理解我们周围的世界尤其至关重要。在发育过程中，突触形成和细化等分子和细胞过程塑造了视觉皮层适当功能的基础电路。因此，清楚地了解支持视觉系统发育的机制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清醒小鼠初级视觉皮层中特定功能反应特性的出现之间的重要联系。 在具体目标 1 中，我将确定从睁眼到成年小鼠视觉皮层中几个基本感受野 (RF) 特性的出现和完善的时间过程。我将使用跨越多层皮层的高密度硅探针测量细胞外单位活动，同时向小鼠呈现优化的视觉刺激。根据这些记录，我将使用最近开发的数据分析技术来量化不同类别细胞（兴奋性、抑制性和特定层）在发育过程中的感受野特性。具体来说，我将描述这些不同细胞类型的方向选择性（OS）、空间频率调谐（SF）和响应线性的个体发育。这将构成第一个完整的发展特征 利用电生理学研究清醒小鼠视觉皮层中的这些射频特性；它将产生新的细胞类型和层特定信息，这些信息是我们实验室和其他实验室未来机制研究所需要的。 在具体目标 2 中，我将从视觉系统中首先出现 OS 的目标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育的特定发育阶段有关。因此，我将检验这样的假设：NR2B 和 NR2A 分别是视觉皮层 (V1) 中几种 RF 特性的建立和后续完善的不同基础。我将在小鼠发育的关键时间点专门测量上述 RF 特性，其中 NR2B 或 NR2A 已从密集占据视觉皮层 IV 层的特定兴奋性细胞群中删除。 这种综合方法将极大地影响我们对视觉系统功能发展机制的理解。具体来说，我们的针对性研究将增加前所未有的机制知识，了解在早期发育过程中建立和完善 V1 反应特性需要 NMDAR 介导的活动的时间和地点。