title: Nitric oxide and cGMP can produce either synaptic depression or potentiation depending on the frequency of presynaptic stimulation in the hippocampus.
abstract: Nitric oxide (NO) has been suggested to play the role of retrograde messenger during long-term potentiation (LTP) in hippocampus. In support of this idea, NO induces LTP when paired with a weak tetanus (50 Hz). An additional criterion that has been proposed for NO being a retrograde messenger is that it should also elicit long-lasting enhancement when paired with low-frequency stimulation of the presynaptic fibers. In the present study, we have tested this prediction. We find that NO produces long-lasting depression rather than potentiation when paired with low-frequency stimulation (0.25 Hz). A similar long-lasting depression is produced by 8-Br-cGMP, a cGMP analog, suggesting that NO may produce its effect by activating soluble guanylyl cyclase. These results demonstrate that NO and cGMP modulate synaptic transmission in the hippocampus by frequency-dependent mechanisms, and suggest that NO is most suitable as a retrograde messenger for LTP when the presynaptic neuron fires at high frequencies. By contrast, carbon monoxide (CO) elicits long lasting enhancement at both low and high frequencies.
authors.affiliation: Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: M
authors.initials: M
authors.lastname: Zhuo
authors.forename: E R
authors.initials: ER
authors.lastname: Kandel
authors.forename: R D
authors.initials: RD
authors.lastname: Hawkins
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D017661:Receptors, Presynaptic / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*
chemical_list: D017661:Receptors, Presynaptic; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006152:Cyclic GMP