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

描述（由申请人提供）：本研究的总体目标是了解视觉皮层中双眼细胞的局部网络如何结合来自左眼和右眼的联合收割机输入。在局部网络水平上理解双眼视觉可能有助于开发新的康复形式，以恢复斜视、弱视或眼睛物理损伤中受损视觉皮层的功能。用于测定皮层神经元的双眼特性的优势方法采用眼优势的单眼测试来推断双眼功能。然而，眼优势和双眼视功能之间的关系仍然不清楚，双眼视功能是立体视觉的关键，只能通过同时刺激双眼来评估。差异调节的功能性微结构从未在任何物种中描述过。此外，虽然在识别单眼剥夺引起的生理和生化变化方面取得了巨大进展，但当眼优势是用于确定双眼的唯一测定法时，存在明显的种间差异（以及同一物种不同研究之间的差异）皮质神经元的特性。通过使用体内双光子钙成像的新技术，本提案的具体目标是确定这些不同的双眼特性是如何映射在皮层回路中的，以评估眼优势和视差调谐的映射之间是否存在系统的关系，并评估这些特性是如何受到单眼剥夺的影响。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，或者这些映射是否与方向选择性所发现的映射一样精确和平滑。在目标2中，我们确定是否存在双目视差的微架构，以及眼优势是否可以预测视差调整。在目标3中，我们研究单眼剥夺是否在关键时期破坏双眼视差的微结构。单眼剥夺后保持正常视差调谐的细胞群集可能为驱动皮层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，我们研究了神经元细胞体钙成像获得的单细胞荧光变化是否与电生理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层回路的功能组织以及改变视觉体验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.