Long-Term Potentiation and Drugs

Abstract

We investigated the modulation of tetanus-induced long-term potentiation (LTP) in guinea pig hippocampal slices brought about by bath-applied drugs and by neurotransmitter-related agents, using an extracellular recording technique. The magnitude of LTP at mossy fiber-CA3 synapses was augmented by the muscarinic receptor agonist carbachol and by endogenous acetylcholine through muscarinic M1 receptors, but the magnitude was attenuated through M2 receptors. Somatostatin augmented mossy fiber LTP; the augmentation was reversed by the muscarinic antagonist scopolamine, suggesting that cholinergic neurons were involved. The magnitude of LTP at mossy fiber-CA3 synapses was augmented by bifemelane and depressed by the opioid antagonist naloxone, but was not affected by the N-methyl-D-aspartate (NMDA) antagonist D-APV (D-2-amino-5-phosphonovalerate). These drugs had no effect on the LTP at fimbrial fiber-CA3 or Schaffer collateral-CAl synapses, except for a blockade evoked by D-APV. We also demonstrated, using the slice-patch technique, that the mossy fiber-CA3 LTP was independent of postsynaptic Ca2+ increase, membrane depolarization, and the activity of G proteins, and that, in contrast, all three of these factors were required for the expression of fimbrial-CA3 LTP. These observations suggest that the LTP at mossy fiber synapses is induced principally by presynaptic mechanisms, and that it is susceptible to various drugs and neurotransmitter-related agents. It is expected that there may be some parallelism between the effects of drugs on mossy fiber-CA3 LTP in vitro and the effects of these drugs on memory function in vivo.