Protein kinase M maintains long-term sensitization and long-term facilitation in aplysia

J Neurosci. 2011 Apr 27;31(17):6421-31. doi: 10.1523/JNEUROSCI.4744-10.2011.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Aplysia / physiology
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Benzophenanthridines / pharmacology
  • Biophysics
  • Biotin / metabolism
  • Brain / cytology*
  • Cell-Penetrating Peptides
  • Cells, Cultured
  • Coculture Techniques / methods
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Lipopeptides / pharmacology
  • Locomotion / drug effects
  • Locomotion / physiology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Memory, Long-Term / drug effects
  • Memory, Long-Term / physiology
  • Models, Neurological
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Oligonucleotides / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Serotonin / pharmacology
  • Statistics, Nonparametric
  • Time Factors

Substances

  • Benzophenanthridines
  • Cell-Penetrating Peptides
  • Enzyme Inhibitors
  • Lipopeptides
  • Oligonucleotides
  • Protein Kinase Inhibitors
  • zeta-inhibitory peptide
  • Serotonin
  • Biotin
  • chelerythrine
  • Protein Kinase C