Tissue regeneration in animals is a remarkable phenomenon, with species such as salamanders and various invertebrates exhibiting extraordinary regenerative capacities in adulthood. While significant progress has been made in uncovering the molecular pathways driving regeneration, a largely unexplored question remains: how does the nervous system dynamically reconfigure itself to restore functionality and behavior in regeneration? This project will address this question by leveraging the exceptional regenerative abilities of the axolotl (Ambystoma mexicanum), in combination with modern approaches in systems and circuit neuroscience. Using retinal regeneration as an experimental model, we will investigate how neural activity, connectivity, and behavior are reorganized throughout the regeneration process. We will use two-photon calcium imaging to track neural activity throughout regeneration in the axolotl’s first visual processing area in the brain, the optic tectum. Longitudinal imaging of the same neurons during visual stimulation will reveal whether critical features of neural encoding, such as retinotopic organization and direction selectivity, are preserved, remodeled, or newly established as the retina regenerates. We will perform detailed histological and structural analyses of the regenerated retina and its projections to the optic tectum to examine the restoration of retinal cell types and topographic mapping of visual inputs. To quantify functional recovery, we will combine behavioral assays, including visually guided prey capture and optomotor reflex tests, with computer vision tools for precise analysis of behavior throughout regeneration. By integrating systems neuroscience, regenerative biology, and cutting-edge neurotechnology, this project aims to uncover the fundamental mechanisms by which the nervous system self-organizes to restore function after injury. These insights will not only advance our understanding of regeneration and plasticity, but also lay the foundation for a new field of research focused on regenerative intelligence, with transformative implications for regenerative medicine and bioengineering.