The superior colliculus is a conserved midbrain structure that converts sensory input into motor output to guide orienting, defensive, and appetitive behaviors. Once regarded as a reflexive sensorimotor relay, it is now recognized as a set of anatomically and functionally distinct circuits defined by cell type, laminar position, projection target, and spatial domain. These circuits form parallel pathways that transform sensory representations into specific motor commands and are dynamically modulated by cortical, subcortical, and state-dependent inputs, providing a structural basis for the flexible adaptation of innate behavioral responses to changing environments, contexts, and brain states. Drawing primarily on work in mice, and using selected findings from primates, birds, and other vertebrates for comparison, we argue that the superior colliculus is organized by three principles: laminar organization, topographic alignment of sensory and motor maps, and modular specialization of cell types and pathways. Together, these principles allow a conserved midbrain structure to generate context-appropriate orienting, approach, and avoidance behaviors across vertebrate species.
Vision is essential for goal-directed locomotion, yet self-generated optic flow during movement through space blurs images, limiting high-acuity vision. One solution that mitigates this challenge for the visual system is aligning specialized regions of the eyes—acute zones or foveae—with optic flow minima, such as the focus of expansion during translation, while keeping periods of rotational optic flow as short as possible. Gaze stability thus arises from coordinated interactions between visual motion processing and precisely timed movements across the body. Although the specific motor programs underlying gaze stabilization vary with behavioral context, they exhibit striking similarities across insect and vertebrate species. Here, we highlight the advantages of studying gaze stabilization in Drosophila melanogaster . The fly's compact central nervous system and its exceptionally well-characterized early visual system enable efforts to link neural signals at the visual periphery with long-range sensorimotor loops that support the adaptive control of gaze stability.
The great diversity of retinal cell types across mammalian species, including humans, is well recognized. Recent transcriptomic profiling has not only confirmed this diversity but also identified homologous cell types across species, revealing molecular conservation of cell type identity. Yet retinal circuits are functionally specialized for distinct visual behaviors across species, raising a key question: If cell types are conserved, then what drives this functional specialization? The answer requires mapping the precise synaptic connections among all cell types—information that has long been difficult to acquire. Here we review, specifically for primates, how artificial intelligence–powered connectomics directly addresses this fundamental question by creating complete retinal connectomes that capture the synaptic connections formed by all cell types within a retinal volume. Recent data from a human foveal connectome suggest that while retinal cell types may be molecularly conserved across human and nonhuman primates, differences in synaptic connectivity drive species-specific functional specialization. Thus, synaptic connectivity, not just cell type identity, drives evolutionary adaptation.
Age-related macular degeneration (AMD) is a multifactorial retinal disease that causes progressive vision loss, with retinal pigment epithelium (RPE) atrophy representing a key initiating event. The RPE monolayer plays a crucial role in maintaining photoreceptor and choriocapillaris health and function. In advanced AMD stages, degeneration extends to the photoreceptors and choriocapillaris, likely as a consequence of preceding RPE atrophy. Existing treatment modalities aim to slow disease progression rather than restore degenerated cells and improve visual function. Pluripotent stem cell–derived RPE cell replacement therapy has emerged as a promising approach for restoring native retinal structure and visual function. This review provides an overview of RPE biology and function, clinical-grade manufacturing of RPE transplants, quality control considerations, and the use of scaffolds to improve delivery and integration. We also summarize preclinical and clinical studies that assess the safety, efficacy, and translational potential of RPE transplantation for AMD and other retinal degenerative conditions.
Neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis, encompass a wide range of chronic conditions with irreversible damage to the central nervous system. Current diagnostic workups of these disorders rely on invasive, time-consuming, and costly tests, such as magnetic resonance imaging and cerebrospinal fluid analysis, preventing accurate decision-making and timely therapeutic interventions. The retina is an extension of the central nervous system; thus, retinal imaging, which is a noninvasive and easily accessible tool, provides a unique window to study brain pathologies. There is a great body of evidence suggesting that neurodegenerative disorders are associated with various structural and vascular problems within the retina. Notably, training machine learning models with retinal images has yielded high levels of accuracy in classifying neurodegenerative diseases, encouraging a new era for early and automated diagnosis of these disorders. This article reviews studies that use such models for classifying these disorders.
