Work is focused on matrix metalloproteases (MMPs), a family of zinc-dependent endopeptidases that can be released and/or activated in a neuronal activity dependent manner. Numerous studies suggest that MMPs play a role in normal learning and memory, though the mechanisms by which they do so are not completely understood. We are particularly interested in their ability to cleave specific synaptic adhesion molecules, their potential to stimulate signaling by G protein coupled protease activated receptors, and their ability to influence population activity through modulation of the perineuronal net. Current work examines proteolysis as a mediator of antidepressant efficacy and ECM attenuation in additional CNS disorders. Studies address the question of whether proteolysis can stimulate excitatory synapse formation and/or reduce inhibitory input to pyramidal cells.