Mechanisms of receptive field establishment in mouse visual cortex

描述（由申请人提供）：视觉主导着人类的感官体验，尤其是视觉皮层对于理解我们周围的世界至关重要。在发育过程中，突触的形成和完善等分子和细胞过程塑造了视觉皮层相应功能的电路。因此，清楚地了解支持视觉系统发展的机制将有助于我们解决损害视觉感知的神经发育障碍。本文提出的工作将为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提供重要的联系。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种基本感受野（RF）特性的出现和完善的时间过程。我将用跨越几层皮层的高密度硅探针测量细胞外单位活动，同时向小鼠提供优化的视觉刺激。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型细胞（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，我将描述定向选择性（OS）、空间频率调谐（SF）和这些不同细胞类型的响应线性的个体发生。这将构成对发展的第一个完整的描述

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.