title: Roles of calcium/calmodulin-dependent kinase II in long-term memory formation in crickets.
abstract: Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a key molecule in many systems of learning and memory in vertebrates, but roles of CaMKII in invertebrates have not been characterized in detail. We have suggested that serial activation of NO/cGMP signaling, cyclic nucleotide-gated channel, Ca(2+)/CaM and cAMP signaling participates in long-term memory (LTM) formation in olfactory conditioning in crickets, and here we show participation of CaMKII in LTM formation and propose its site of action in the biochemical cascades. Crickets subjected to 3-trial conditioning to associate an odor with reward exhibited memory that lasts for a few days, which is characterized as protein synthesis-dependent LTM. In contrast, animals subjected to 1-trial conditioning exhibited memory that lasts for only several hours (mid-term memory, MTM). Injection of a CaMKII inhibitor prior to 3-trial conditioning impaired 1-day memory retention but not 1-hour memory retention, suggesting that CaMKII participates in LTM formation but not in MTM formation. Animals injected with a cGMP analogue, calcium ionophore or cAMP analogue prior to 1-trial conditioning exhibited 1-day retention, and co-injection of a CaMKII inhibitor impaired induction of LTM by the cGMP analogue or that by the calcium ionophore but not that by the cAMP analogue, suggesting that CaMKII is downstream of cGMP production and Ca(2+) influx and upstream of cAMP production in biochemical cascades for LTM formation. Animals injected with an adenylyl cyclase (AC) activator prior to 1-trial conditioning exhibited 1-day retention. Interestingly, a CaMKII inhibitor impaired LTM induction by the AC activator, although AC is expected to be a downstream target of CaMKII. The results suggest that CaMKII interacts with AC to facilitate cAMP production for LTM formation. We propose that CaMKII serves as a key molecule for interplay between Ca(2+) signaling and cAMP signaling for LTM formation, a new role of CaMKII in learning and memory.
authors.affiliation: Faculty of Science, Hokkaido University, Sapporo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Mizunami
authors.affiliation: Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nemoto
authors.affiliation: Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Kanta
authors.initials: K
authors.lastname: Terao
authors.affiliation: Faculty of Science, Hokkaido University, Sapporo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hamanaka
authors.affiliation: Faculty of Science, Hokkaido University, Sapporo, Japan; Faculty of Liberal Arts, Tokyo Medical and Dental University, Ichikawa, Japan.
authors.forename: Yukihisa
authors.initials: Y
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006135:Gryllidae / Q000201:enzymology* / Q000502:physiology; D007858:Learning / Q000502:physiology; D057567:Memory, Long-Term / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D009569:Nitric Oxide; D000242:Cyclic AMP; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D006152:Cyclic GMP; D002118:Calcium