Caspase activity plays an essential role in long-term memory.

Activation of intracellular second messenger cascades has been linked to learning and memory in various organisms. Identification of down-stream targets of these second messengers that play a role in learning and memory is an active area of research. Recently, it has been reported that increases in intracellular calcium can activate a cysteine-dependent aspartate-directed protease (caspase) cascade in mice. Using an antibody that selectively recognizes activated caspase-3, we detected the presence of this enzyme in hippocampal neurons. Inhibition of caspase activity in the hippocampus blocked long-term, but not short-term, spatial memory. These results suggest that a caspase-mediated cellular event(s) in hippocampal neurons is critical for long-term spatial memory storage.