Matrix metalloproteinases (MMPs) are key modulators of the extracellular matrix (ECM) and play a critical role in synaptic remodeling within the hippocampus. Their activity influences synaptic plasticity, learning, and memory by regulating structural and functional changes at synapses. Long-term potentiation (LTP), a long-lasting enhancement in synaptic transmission induced by high-frequency stimulation, serves as a widely accepted model for activity-dependent synaptic plasticity and a neuronal correlate of learning and memory. Impairments in hippocampal LTP have been closely linked to deficits in behavioral learning and memory, highlighting the importance of ECM regulation by MMPs in cognitive processes. This study investigates the effects of MMP inhibition on long-term plasticity at perforant pathway–dentate gyrus synapses in vivo, aiming to elucidate the molecular mechanisms by which MMPs contribute to synaptic function and cognitive performance. Understanding the role of MMPs in hippocampal plasticity provides insights into potential therapeutic strategies for cognitive disorders associated with synaptic dysfunction.