Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia.
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.
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States.
Shanping
S
Chen
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States.
Diancai
D
Cai
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States.
Kaycey
K
Pearce
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States.
Philip Y-W
PY
Sun
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States.
Adam C
AC
Roberts
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States.
David L
DL
Glanzman
D000818:Animals; D001048:Aplysia / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D053119:Benzophenanthridines / Q000494:pharmacology; D018920:Coculture Techniques; D044127:Epigenesis, Genetic / Q000187:drug effects; D006655:Histone Deacetylases / Q000378:metabolism; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D018613:Microscopy, Confocal; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D000099221:Protein Kinase C zeta
D053119:Benzophenanthridines; D006655:Histone Deacetylases; D011493:Protein Kinase C; D012701:Serotonin; D000099221:Protein Kinase C zeta; C016299:chelerythrine
Aplysia californica; epigenetics; long-term memory; memory reconsolidation; neuroscience; protein kinase Mζ; synaptic structure