Inhibition of caspase-3 blocks long-term potentiation in hippocampal slices.

Incubation of rat hippocampal slices with the specific caspase-3 inhibitor Z-DEVD-FMK led to suppression of long-term potentiation (LTP), which developed over a period of time. Incubation of Z-DEVD-FMK for 4 h and more prevented tetanization from evoking LTP; Z-DEVD-FMK had no effect on baseline measures of synaptic plasticity and short-term plasticity (population spike amplitude, level of facilitation in conditions of paired stimuli). These data provide the first evidence for the involvement of a mechanism mediated by caspase-3 in the phenomenon of LTP.