Multimodal approaches to visual experimental research: Imaging, electrophysiology, and behavior

Although vision is one of the primary senses in humans, direct mechanistic research in patients is challenging both technically and ethically because of its multiscale complexity-spanning phototransduction, neural processing, and perception. The foundation of visual science is animal models, which offer controlled, systematic assess to every stage of the visual pathway. Animal models' visual phenotyping methods are highly significant for vision-related research. However, the selection of various experimental methods and critical differences between them are frequently disregarded in study design. To address this, we present a systematic paradigm for in vivo visual phenotyping built upon three complementary pillars: imaging, electrophysiology, and behavioral testing. This triad reveals the integrity of the visual pathway from structural, functional, and perceptual perspectives, respectively. This review details the methodological principles of each visual phenotyping approach and advocates for integrative analytical strategies that connect macroscopic visual deficiencies to microcircuit dysfunction. By setting clear guidelines for multimodal data fusion and translational benchmarking, this paradigm aims to accelerate mechanism-based pathological investigation and therapeutic development. Ultimately, it will help advance the field from descriptive phenomenology toward a predictive, integrative phenomics. These convergent approaches are essential for strengthening the bridge between animal studies and clinical applications, thereby accelerating the delivery of novel treatments to patients with visual impairments.