We reported previously that orphanin FQ (OFQ) inhibited NMDA receptor-media
ted synaptic currents and consequently suppressed induction of long-term po
tentiation (LTP) in the hippocampal dentate gyrus. This study examines the
effect of OFQ on several other forms of long-term synaptic plasticity in th
e lateral perforant path of mouse hippocampal dentate gyrus. (1) Long-term
depression (LTD): a low frequency stimulation (1 Hz, 15 min) applied to the
lateral perforant path induced a long-lasting reduction in the dentate fie
ld potentials in slices from 22- to 30-day-old mice. This LTD was sensitive
to the NMDA receptor blocker D-APS, and could be significantly attenuated
by bath application of OFQ (1 mu M, 25 min). (2) Primed LTD: induction of L
TD in slices from 50- to 65-day-old mice required a priming procedure consi
sting of multiple high frequency stimulus trains delivered in the presence
of D-APS before the low-frequency stimulation. OFQ applied during the low-f
requency stimulation, but not during the priming trains, blocked induction
of primed LTD. (3) Depotentiation: high-frequency train-induced dentate LTP
could be reversed by a subsequent low-frequency stimulation. This depotent
iation was also attenuated by either OFQ or D-APS applied during low-freque
ncy stimulation. These results, together with our previous findings, sugges
t that OFQ inhibits bidirectional changes in synaptic strength in the denta
te; and its multiple actions on NMDA receptor-dependent, long-term synaptic
plasticity might work in tandem to regulate hippocampus-dependent learning
and memory.