Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia

Elife. 2014 Nov 17;3:e03896. doi: 10.7554/eLife.03896.


Long-term memory (LTM) is believed to be stored in the brain as changes in synaptic connections. Here, we show that LTM storage and synaptic change can be dissociated. Cocultures of Aplysia sensory and motor neurons were trained with spaced pulses of serotonin, which induces long-term facilitation. Serotonin (5HT) triggered growth of new presynaptic varicosities, a synaptic mechanism of long-term sensitization. Following 5HT training, two antimnemonic treatments-reconsolidation blockade and inhibition of PKM--caused the number of presynaptic varicosities to revert to the original, pretraining value. Surprisingly, the final synaptic structure was not achieved by targeted retraction of the 5HT-induced varicosities but, rather, by an apparently arbitrary retraction of both 5HT-induced and original synapses. In addition, we find evidence that the LTM for sensitization persists covertly after its apparent elimination by the same antimnemonic treatments that erase learning-related synaptic growth. These results challenge the idea that stable synapses store long-term memories.

Keywords: Aplysia californica; epigenetics; long-term memory; memory reconsolidation; neuroscience; protein kinase Mζ; synaptic structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Aplysia / drug effects
  • Aplysia / enzymology
  • Aplysia / physiology*
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Benzophenanthridines / pharmacology
  • Coculture Techniques
  • Epigenesis, Genetic / drug effects
  • Histone Deacetylases / metabolism
  • Memory, Long-Term / drug effects
  • Memory, Long-Term / physiology*
  • Microscopy, Confocal
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Serotonin / pharmacology
  • Synapses / drug effects
  • Synapses / physiology*


  • Benzophenanthridines
  • Serotonin
  • chelerythrine
  • protein kinase C zeta
  • Protein Kinase C
  • Histone Deacetylases