Novel Models of Visual Topographic Map Alignment in the Superior Colliculus

The establishment of precise neuronal connectivity during development is critical for sensing the external environment and informing appropriate behavioral responses. In the visual system, many connections are organized topographically, which preserves the spatial order of the visual scene. The superior colliculus (SC) is a midbrain nucleus that integrates visual inputs from the retina and primary visual cortex (V1) to regulate goal-directed eye movements. In the SC, topographically organized inputs from the retina and V1 must be aligned to facilitate integration. Previously, we showed that retinal input instructs the alignment of V1 inputs in the SC in a manner dependent on spontaneous neuronal activity; however, the mechanism of activity-dependent instruction remains unclear. To begin to address this gap, we developed two novel computational models of visual map alignment in the SC that incorporate distinct activity-dependent components. First, a Correlational Model assumes that V1 inputs achieve alignment with established retinal inputs through simple correlative firing mechanisms. A second Integrational Model assumes that V1 inputs contribute to the firing of SC neurons during alignment. Both models accurately replicate in vivo findings in wild type, transgenic and combination mutant mouse models, suggesting either activity-dependent mechanism is plausible. In silico experiments reveal distinct behaviors in response to weakening retinal drive, providing insight into the nature of the system governing map alignment depending on the activity-dependent strategy utilized. Overall, we describe novel computational frameworks of visual map alignment that accurately model many aspects of the in vivo process and propose experiments to test them.发育过程中精确神经元连接的建立对于感知外部环境并指导适当的行为反应至关重要。在视觉系统中，众多连接以拓扑方式组织，从而保留了视觉场景的空间顺序。上丘（SC）是中脑核团之一，它整合来自视网膜和初级视觉皮层（V1）的视觉输入以调节目标导向的眼球运动。在上丘中，来自视网膜和V1的拓扑组织输入必须对齐以促进整合。此前，我们曾展示视网膜输入通过依赖自发性神经元活动的方式指导SC中V1输入的对齐；然而，活动依赖性指导的机制尚不明确。为了填补这一空白，我们开发了两种新颖的计算模型，用于SC中视觉地图对齐，并融入了不同的活动依赖性成分。首先，相关模型假定V1输入通过简单的相关性触发机制与已建立的视网膜输入实现对齐。其次，整合模型假定V1输入在对齐过程中对SC神经元的触发有所贡献。这两个模型均能准确复制野生型、转基因和组合突变小鼠模型中的体内发现，表明活动依赖性机制是可行的。计算机模拟实验揭示了在视网膜驱动减弱时的不同行为，为根据活动依赖性策略所采用的系统调控地图对齐的实质提供了洞见。总体而言，我们描述了视觉地图对齐的新颖计算框架，这些框架准确模拟了体内过程的许多方面，并提出了测试这些框架的实验。