Long-term potentiation in the hippocampus in conditions of inhibition of caspase-3: analysis of facilitation in paired-pulse stimulation.

Treatment of hippocampal slices with the caspase-3 inhibitor Z-DEVD-FMK led to a decrease in the magnitude of long-term potentiation (LTP), which developed over time. Testing with paired stimuli separated by an interval of 70 msec showed that after caspase-3 inhibition, as compared with control slices, the second response in the pair showed no increase in amplitude in conditions of LTP. In these conditions, the magnitude of LTP depended on differences in the amplitudes of the first and second responses before induction of LTP. LTP was absent in slices with initially highly efficient afferent stimulation and correspondingly low levels of facilitation in paired-pulse stimulation. It is suggested that inhibition of caspase-3 prevents the structural rearrangements in LTP associated with the involvement of new synapses and neurons in the response.