Activity-dependent refinement of nasal retinal projections drives topographic map sharpening in the teleost visual system

ABSTRACT Topographic maps in the brain are essential for processing information. Yet, our understanding of topographic mapping has remained limited by our inability to observe maps forming and refining directly in vivo. Here, we used Cre-mediated recombination of a new colorswitch reporter in zebrafish to generate the first transgenic model allowing the dynamic analysis of retinotopic mapping in vivo. We found that the antero-posterior retinotopic map forms early but remains dynamic, with nasal and temporal retinal axons expanding their projection domains over time. Nasal projections initially arborize in the anterior tectum but progressively refine their projection domain to the posterior tectum in an activity-dependent manner. This activity-dependent refinement drives retinotopic map sharpening along the antero-posterior axis. Altogether, our study provides the first analysis of a topographic map maturing in real-time in a live animal and opens new strategies for dissecting the intricate mechanisms of precise topographic mapping in vertebrates.