Perineuronal nets (PNNs), a specialized form of the extracellular matrix, enwrap subtypes of neurons and have many proposed functions including regulating adult brain plasticity. Removal of PNNs in adult mice by the bacterial enzyme chondroitinase ABC restores brain plasticity levels to that of juveniles. However, chondroitinase ABC indiscriminately degrades all chondroitin sulfate proteoglycans in the extracellular matrix, its effect is not restricted to PNNs. In contrast, several endogenous metalloproteinases specifically target PNN components. Some of these are selectively expressed in PNN-enwrapped neurons, indicating a role in the regulation of PNNs in the brain. Here, we aim to tap into these endogenous regulators of PNNs. We hypothesize that the upregulation of specific genes could be sufficient for degrading PNNs and consequently, lifting the brakes on adult brain plasticity. We introduce and amplify targeted genes conjugated with fluorescent proteins using adeno-associated virus (AAV) vectors to visualize and track the impact on PNNs in transduced cells. To measure the effects on neural population dynamics and brain plasticity, soma-targeted genetically encoded calcium indicators are co-injected to allow direct assessment of neuronal activity and changes in plasticity. We are currently analyzing the efficacy of known aggrecanases expressed in the brain that are upregulated in neurons associated with PNNs, as well as various PNN modifying genes. By dissecting these endogenous pathways, our research aims to present a nuanced understanding of PNN dynamics and contribute to a more targeted approach for manipulating neural plasticity, with potential implications for rehabilitative strategies in neural injuries or disorders.