title: Critical role of nitric oxide-cGMP cascade in the formation of cAMP-dependent long-term memory.
abstract: Cyclic AMP pathway plays an essential role in formation of long-term memory (LTM). In some species, the nitric oxide (NO)-cyclic GMP pathway has been found to act in parallel and complementary to the cAMP pathway for LTM formation. Here we describe a new role of the NO-cGMP pathway, namely, stimulation of the cAMP pathway to induce LTM. We have studied the signaling cascade underlying LTM formation by systematically coinjecting various "LTM-inducing" and "LTM-blocking" drugs in crickets. Multiple-trial olfactory conditioning led to LTM that lasted for several days, while memory induced by single-trial conditioning decayed away within several hours. Injection of inhibitors of the enzyme forming NO, cGMP, or cAMP into the hemolymph prior to multiple-trial conditioning blocked LTM, whereas injection of an NO donor, cGMP analog, or cAMP analog prior to single-trial conditioning induced LTM. Induction of LTM by injection of an NO donor or cGMP analog paired with single-trial conditioning was blocked by inhibitors of the cAMP pathway, but induction of LTM by a cAMP analog was unaffected by inhibitors of the NO-cGMP pathway. Inhibitors of cyclic nucleotide-gated channel (CNG channel) or calmodulin-blocked induction of LTM by cGMP analog paired with single-trial conditioning, but they did not affect induction of LTM by cAMP analog. Our findings suggest that the cAMP pathway is a downstream target of the NO-cGMP pathway for the formation of LTM, and that the CNG channel and calcium-calmodulin intervene between the NO-cGMP pathway and the cAMP pathway.
authors.affiliation: Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai 980-8577, Japan.
authors.forename: Yukihisa
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Sae
authors.initials: S
authors.lastname: Unoki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Aonuma
authors.forename: Makoto
authors.initials: M
authors.lastname: Mizunami
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D006135:Gryllidae; D008297:Male; D008568:Memory / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D012903:Smell / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D000242:Cyclic AMP; D006152:Cyclic GMP