Activation of intracellular second messenger cascades has been linked to le
arning and memory in various organisms. Identification of down-stream targe
ts 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 reco
gnizes activated caspase-3, we detected the presence of this enzyme in hipp
ocampal neurons. Inhibition of caspase activity in the hippocampus blocked
longterm, but not short-term, spatial memory. These results suggest that a
caspase-mediated cellular event(s) in hippocampal neurons is critical for l
ong-term spatial memory storage. (C) 2000 Lippincott Williams & Wilkins.