ENDOGENOUS OPIOIDS REGULATE LONG-TERM POTENTIATION OF SYNAPTIC INHIBITION IN THE DENTATE GYRUS OF RAT HIPPOCAMPUS

Long-term potentiation (LTP) of excitatory transmission in the hippoca mpus has been extensively studied as a synaptic model of learning and memory, Here we report a new form of LTP in which inhibitory synaptic signals are potentiated following tetanic stimulation of an opioid-con taining excitatory pathway in the presence of opioid antagonists, The lateral perforant path (LPP) was stimulated at the dentate outer molec ular layer of hippocampal slices, Evoked synaptic currents were record ed from dentate granule cells using whole-cell voltage-clamp technique s, A high-frequency stimulus train (100 Hz, 1 sec) delivered to the LP P in the presence of naloxone (1 mu M) was found to induce a long-last ing potentiation (20 min to 2 hr) in the amplitude of gamma-aminobutyr ic acid(A) (GABA(A)) receptor-mediated inhibitory postsynaptic current s (IPSCs) of granule cells, Such a potentiation was not observed when tetanizing the LPP in control medium, Naloxone-revealed LTP of LPP-evo ked IPSCs did not depend upon the presence of granule cell discharge, and was not accompanied by potentiation of messy fiber-evoked IPSCs, i ndicating that feedforward, but not feedback, inhibitory circuits were involved, Induction of this LTP could be completely blocked by the N- methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopen tanoic acid (D-APV). However, it was not significantly affected by hyp erpolarization of granule cells, These results suggest that LTP may oc cur at the excitatory synapses between LPP terminals and GABAergic int erneurons, rather than at the inhibitory synapses between interneurons and granule cells, Further examination using selective opioid antagon ists demonstrated that blocking delta, but not mu and kappa, receptors is critical for inducing LTP of IPSCs in granule cells.