Temporally distinct pre- and post-synaptic mechanisms maintain long-term potentiation

LONG-TERM potentiation (LTP) in the hippocampus is widely studied as the mechanisms involved in its induction and maintenance are believed to underlie fundamental properties of learning and memory in vertebrates1. Most synapses that exhibit LTP use an excitatory amino-acid neurotransmitter that acts on two types of receptor, the N-methyl-D-aspartate (NMDA) and quisqualate receptors2. The quisqualate receptor mediates the fast synaptic response evoked by low-frequency stimulation3,4, whereas the NMDA receptor system is activated transiently by tetanic stimulation, leading to the induction of LTP3,5–7. The events responsible for maintaining LTP once it is established are not known. We now demonstrate that the sensitivity of CA1 neurons in hippocampal slices to ionophoretically-applied quisqualate receptor ligands slowly increases following the induction of LTP. This provides direct evidence for a functional post-synaptic change and suggests that pre-synaptic mechanisms also contribute, but in a temporally distinct manner, to the maintenance of LTP.

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