• cortical plasticity
• genetic labeling
• perineuronal nets
• two-photon microscopy
• visual cortex

The complexity of the nervous system manifests itself across various spatial and temporal scales. This calls for the development of equally sophisticated tools to holistically understand the system. Recently, there has been an increasing number of investigations at the level of neural circuits in the cortex. This fascination has unveiled the critical role played by the extracellular matrix (ECM) in shaping cortical neural circuits in response to experience. Perineuronal nets (PNNs) are specialized aggregates of the ECM enveloping the cell bodies and dendrites of diverse mammalian neuronal cell types, pivotal in this circuitry remodeling process. Moreover, accumulating evidence underscores their involvement in a multitude of other physiological and pathological processes spanning numerous disciplines and fields. Despite the burgeoning importance of PNNs, a significant gap exists in our ability to visualize and dissect the structural and functional dynamics of these long-overlooked structures. Addressing this shortfall, our study introduces an innovative genetic tool that merges a fluorescent protein with the Hapln1 protein, a key constituent of PNNs. This fusion empowers researchers with the means to visualize PNNs with high precision and detail not only in the spatial but also across the temporal domain, allowing for longitudinal study using two-photon microscopy. By bridging this technological gap, our work opens new avenues for studying the intricate role of PNNs in the nervous system, offering fresh insights into their contributions to neurological function and dysfunction.