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Activity-dependent long-term enhancement of transmitter release by presynaptic 3′,5′-cyclic GMP in cultured hippocampal neurons

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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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Authors and Affiliations

  1. Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, and Howard Hughes Medical Institute, 722 West 168th Street, New York, New York, 10032, USA

    O. Arancio, E. R. Kandel & R. D. Hawkins

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  1. O. Arancio
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  2. E. R. Kandel
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  3. R. D. Hawkins
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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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