Abstract
LONG–TERM potentiation (LTP) in hippocampus is a type of synap-tic plasticity that is thought to be involved in learning and memory1. Several lines of evidence suggest that LTP involves 3′,5′-cyclic GMP (cGMP), perhaps as an activity-dependent presynaptic effector of one or more retrograde messengers (refs 2-12, but see ref. 13). However, previous results are also consistent with postsynaptic effects of cGMP. This is difficult to test in hippocam-pal slices, but more rigorous tests are possible in dissociated cell culture14–17. We have therefore developed a reliable method for producing N-methyl-D-aspartate (NMDA) receptor-dependent LTP at synapses between individual hippocampal pyramidal neurons in culture. We report that inhibitors of guanylyl cyclase or of cGMP-dependent protein kinase block potentiation by either tetanic stimulation or low-frequency stimulation paired with postsynaptic depolarization. Conversely, application of 8-Br-cGMP to the bath or injection of cGMP into the presynaptic neuron produces activity-dependent long-lasting potentiation. The potentiation by cGMP involves an increase in transmitter release that is in part independent of changes in the presynaptic action potential. These results support a presynaptic role for cGMP in LTP.
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Arancio, O., Kandel, E. & Hawkins, R. Activity-dependent long-term enhancement of transmitter release by presynaptic 3′,5′-cyclic GMP in cultured hippocampal neurons. Nature 376, 74–80 (1995). https://doi.org/10.1038/376074a0
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DOI: https://doi.org/10.1038/376074a0
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