Blockade of long-term depression in neonatal hippocampal slices by a phospholipase A2 inhibitor.

Low-frequency stimulation of the Schaffer-commissural pathways in slices prepared from juvenile rats (postnatal day 10-15) results in a long-term depression (LTD) of synaptic transmission. 30 min after 5 min of stimulation at 5 Hz, the response to the stimulated pathway was decreased by 36%, whereas the response to an unstimulated pathway projecting to the same neuronal population was decreased by 20%. Stimulation in the presence of the NMDA receptor antagonist AP5 completely prevented homosynaptic LTD. The phospholipase A2 inhibitor, bromophenacylbromide, also significantly reduced the extent of LTD in both the stimulated and control pathways. LTD was accompanied by a decrease in paired-pulse facilitation, suggesting a change in transmitter release. It also resulted in an increased effect of iontophoretically applied perchlorate, an ion which increases both the affinity of glutamate for the synaptic alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionate (AMPA) receptors and synaptic responses, suggesting a change in postsynaptic receptors. These findings indicate that certain stimulation paradigms produce a combination of pre- and postsynaptic modifications that could underlie changes in synaptic efficacy.