Development and plasticity of functional micro-organization of the visual cortex

描述(申请人提供)：这项研究的总体目标是了解视觉皮质中双眼细胞的局部网络如何结合来自左眼和右眼的输入。在局部网络水平上了解双眼视觉可能有助于发展新的康复形式，以恢复斜视、弱视或眼睛物理损伤患者受损的视觉皮质的功能。分析皮质神经元的双眼特性的主要方法是使用单眼优势测试来推断双眼功能。然而，眼睛优势和双眼视差之间的关系仍然不清楚--这一特性对立体视觉至关重要，只能通过同时刺激双眼来评估。视差调节的功能微体系结构从未在任何物种中被描述过。此外，虽然在确定单眼剥夺引起的生理和生化变化方面取得了很大进展，但当眼优势是唯一用于确定皮质神经元双眼特性的方法时，存在明显的物种间差异(以及同一物种中不同研究之间的差异性)。通过使用体内双光子钙成像的新技术，这项建议的具体目标是确定这些不同的双眼属性是如何在大脑皮层环路中映射的，评估眼睛优势映射和视差调节之间是否存在系统关系，以及评估单眼剥夺如何影响这些属性。在目标1中，我们将解决是否存在来自不同眼优势组的神经元的局部混合，或者这些图是否像那些发现的定向选择性一样精确和平滑。在目标2中，我们确定双眼视差的微结构是否存在，以及眼睛优势是否可以预测视差调节。在目标3中，我们研究了关键期的单眼剥夺是否会破坏双眼视差的微结构。单眼剥夺后保持正常视差调节的细胞的聚集可能为了解驱动皮质神经元成为视差选择性的局部电路机制提供重要线索。在目标4中，我们检查了神经元胞体钙成像获得的单细胞荧光变化是否与电生理学方法获得的单细胞放电率相关。这些结果有望为调节双眼视觉的皮质环路的功能组织以及视觉体验改变的有害影响提供新的线索。

DESCRIPTION (provided by applicant): The overall goal of this research is to understand how local networks of binocular cells in the visual cortex combine inputs from the left and right eyes. Understanding binocular vision at the local network level may contribute to the development of new forms of rehabilitation for restoring function to the compromised visual cortex in strabismus, amblyopia, or physical damage to the eye. The dominant approach for assaying the binocular properties of cortical neurons employs monocular tests of ocular dominance to infer binocular function. However, the relationship between ocular dominance and binocular disparity-a property that is critical for stereopsis and can only be assessed with simultaneous stimulation of both eyes-remains unclear. The functional micro-architecture of disparity tuning has never been described in any species. Furthermore, while great strides have been made in identifying the physiological and biochemical changes that result from monocular deprivation, there are clear inter-species differences (and variability amongst different studies in the same species) when ocular dominance is the only assay used to determine the binocular properties of cortical neurons. By using the new technique of two-photon calcium imaging in vivo, the specific goals of this proposal are to determine how these distinct binocular properties are mapped in cortical circuits, to assess whether there are systematic relationships between the mapping of ocular dominance and disparity tuning, and to evaluate how these properties are impacted by monocular deprivation. In Aim 1, we will resolve whether there is local mixing of neurons from different ocular dominance groups or whether these maps are as precise and smooth as those found for orientation selectivity. In Aim 2, we determine whether a micro-architecture for binocular disparity exists and whether ocular dominance can predict disparity tuning. In Aim 3, we examine whether monocular deprivation during the critical period disrupts the micro-architecture of binocular disparity. Clustering of cells that retain normal disparity tuning after monocular deprivation may provide important clues into the local circuit mechanisms that drive cortical neurons to become disparity selective. In Aim 4, we examine whether the single-cell fluorescence changes obtained with calcium imaging of neuronal cell bodies correlate with the single-cell firing rates obtained with electrophysiological methods. These results promise to shed new light on the functional organization of cortical circuits that mediate binocular vision, and the detrimental effects of altered visual experience.