title: Intermediate-term memory for site-specific sensitization in aplysia is maintained by persistent activation of protein kinase C.
abstract: Recent studies of long-term synaptic plasticity and long-term memory have demonstrated that the same functional endpoint, such as long-term potentiation, can be induced through distinct signaling pathways engaged by different patterns of stimulation. A critical question raised by these studies is whether different induction pathways either converge onto a common molecular mechanism or engage different molecular cascades for the maintenance of long-term plasticity. We directly examined this issue in the context of memory for sensitization in the marine mollusk Aplysia. In this system, training with a single tail shock normally induces short-term memory (<30 min) for sensitization of tail-elicited siphon withdrawal, whereas repeated spaced shocks induce both intermediate-term memory (ITM) (>90 min) and long-term memory (>24 hr). We now show that a single tail shock can also induce ITM that is expressed selectively at the trained site (site-specific ITM). Although phenotypically similar to the form of ITM induced by repeated trials, the mechanisms by which site-specific ITM is induced and maintained are distinct. Unlike repeated-trial ITM, site-specific ITM requires neither protein synthesis nor PKA activity for induction or maintenance. Rather, the induction of site-specific ITM requires calpain-dependent proteolysis of activated PKC, yielding a persistently active PKC catalytic fragment (PKM) that also serves to maintain the memory in the intermediateterm temporal domain. Thus, two unique forms of ITM that have different induction requirements also use distinct molecular mechanisms for their maintenance.
authors.affiliation: Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut 06520-8074, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sutton
authors.forename: Martha W
authors.initials: MW
authors.lastname: Bagnall
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Justin
authors.initials: J
authors.lastname: Shobe
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carew
mesh_terms: D000818:Animals; D001048:Aplysia / Q000502:physiology*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D004597:Electroshock; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012018:Reflex / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009281:Naphthalenes; D011493:Protein Kinase C; D002154:Calpain; C058819:calphostin C