title: Protein kinase M maintains long-term sensitization and long-term facilitation in aplysia.
abstract: How the brain maintains long-term memories is one of the major outstanding questions in modern neuroscience. Evidence from mammalian studies indicates that activity of a protein kinase C (PKC) isoform, protein kinase Mζ (PKMζ), plays a critical role in the maintenance of long-term memory. But the range of memories whose persistence depends on PKMζ, and the mechanisms that underlie the effect of PKMζ on long-term memory, remain obscure. Recently, a PKM isoform, known as PKM Apl III, was cloned from the nervous system of Aplysia. Here, we tested whether PKM Apl III plays a critical role in long-term memory maintenance in Aplysia. Intrahemocoel injections of the pseudosubstrate inhibitory peptide ZIP (ζ inhibitory peptide) or the PKC inhibitor chelerythrine erased the memory for long-term sensitization (LTS) of the siphon-withdrawal reflex (SWR) as late as 7 d after training. In addition, both PKM inhibitors disrupted the maintenance of long-term (≥ 24 h) facilitation (LTF) of the sensorimotor synapse, a form of synaptic plasticity previously shown to mediate LTS of the SWR. Together with previous results (Bougie et al., 2009), our results support the idea that long-term memory in Aplysia is maintained via a positive-feedback loop involving PKM Apl III-dependent protein phosphorylation. The present data extend the known role of PKM in memory maintenance to a simple and well studied type of long-term learning. Furthermore, the demonstration that PKM activity underlies the persistence of LTF of the Aplysia sensorimotor synapse, a form of synaptic plasticity amenable to rigorous cellular and molecular analyses, should facilitate efforts to understand how PKM activity maintains memory.
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, College, Los Angeles, California 90095-1606, USA.
authors.forename: Diancai
authors.initials: D
authors.lastname: Cai
authors.forename: Kaycey
authors.initials: K
authors.lastname: Pearce
authors.forename: Shanping
authors.initials: S
authors.lastname: Chen
authors.forename: David L
authors.initials: DL
authors.lastname: Glanzman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001048:Aplysia / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D053119:Benzophenanthridines / Q000494:pharmacology; D001703:Biophysics; D001710:Biotin / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D057846:Cell-Penetrating Peptides; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D055666:Lipopeptides / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology; D008959:Models, Neurological; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009841:Oligonucleotides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D053119:Benzophenanthridines; D057846:Cell-Penetrating Peptides; D004791:Enzyme Inhibitors; D055666:Lipopeptides; D009841:Oligonucleotides; D047428:Protein Kinase Inhibitors; C568285:zeta-inhibitory peptide; D012701:Serotonin; D001710:Biotin; C016299:chelerythrine; D011493:Protein Kinase C