CREB in the Pond Snail Lymnaea stagnalis: Cloning, Gene Expression and Function in Identifiable Neurons of the Central Nervous System

Hisayo Sadamoto, Hanae Sato, Suguru Kobayashi, Jun Murakami, Hitoshi Aonuma, Hironori Ando, Yutaka Fujito, Kaoru Hamano, Masahiko Awaji, Ken Lukowiak, Akihisa Urano, Etsuro Ito

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


The pond snail Lymnaea stagnalis is an excellent model system in which to study the neuronal and molecular substrates of associative learning and its consolidation into long-term memory. Until now, the presence of cyclic AMP (cAMP)-responsive element binding protein (CREB), which is believed to be a necessary component in the process of a learned behavior that is consolidated into long-term memory, has only been assumed in Lymnaea neurons. We therefore cloned and analyzed the cDNA sequences of homologues of CREB1 and CREB2 and determined the presence of these mRNAs in identifiable neurons of the central nervous system (CNS) of L. stagnalis. The deduced amino acid sequence of Lymnaea CREB1 is homologous to transcriptional activators, mammalian CREB1 and Aplysia CREB1a, in the C-terminal DNA binding (bZIP) and phosphorylation domains, whereas the deduced amino acid sequence of Lymnaea CREB2 is homologous to transcriptional repressors, human CREB2, mouse activating transcription factor-4, and Aplysia CREB2 in the bZIP domain. In situ hybridization revealed that only a relatively few neurons showed strongly positive signals for Lymnaea CREB1 mRNA, whereas all the neurons in the CNS contained Lymnaea CREB2 mRNA. Using one of the neurons (the cerebral giant cell) containing Lymnaea CREB1 mRNA, we showed that the injection of a CRE oligonucleotide inhibited a cAMP-induced, long-lasting synaptic plasticity. We therefore conclude that CREBs are present in Lymnaea neurons and may function as necessary players in behavioral plasticity.

Original languageEnglish (US)
Pages (from-to)455-466
Number of pages12
JournalJournal of Neurobiology
Issue number4
StatePublished - Mar 2004
Externally publishedYes


  • Associative learning
  • Cerebral giant cell
  • Cyclic AMP
  • Facilitation
  • Long-term memory

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience


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