Identification of a serotonin receptor coupled to adenylyl cyclase involved in learning-related heterosynaptic facilitation in Aplysia

Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14634-9. doi: 10.1073/pnas.0907502106. Epub 2009 Aug 11.


Serotonin (5-HT) plays a critical role in modulating synaptic plasticity in the marine mollusc Aplysia and in the mammalian nervous system. In Aplysia sensory neurons, 5-HT can activate several signal cascades, including PKA and PKC, presumably via distinct types of G protein-coupled receptors. However, the molecular identities of these receptors have not yet been identified. We here report the cloning and functional characterization of a 5-HT receptor that is positively coupled to adenylyl cyclase in Aplysia neurons. The cloned receptor, 5-HT(apAC1), stimulates the production of cAMP in HEK293T cells and in Xenopus oocytes. Moreover, the knockdown of 5-HT(apAC1) expression by RNA interference blocked 5-HT-induced cAMP production in Aplysia sensory neurons and blocked synaptic facilitation in nondepressed or partially depressed sensory-to-motor neuron synapses. These data implicate 5-HT(apAC1) as a major modulator of learning related synaptic facilitation in the direct sensory to motor neuron pathway of the gill withdrawal reflex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Aplysia / cytology
  • Aplysia / genetics
  • Aplysia / physiology*
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Chromosome Pairing / physiology*
  • Cloning, Molecular
  • Cyclic AMP / metabolism
  • Female
  • Humans
  • In Situ Hybridization
  • Learning / physiology*
  • Membrane Potentials
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Oocytes / physiology
  • Phylogeny
  • Receptors, Serotonin / classification
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / physiology*
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / metabolism
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Serotonin / pharmacology
  • Transfection
  • Xenopus laevis


  • Receptors, Serotonin
  • Serotonin
  • Cyclic AMP
  • Adenylyl Cyclases

Associated data

  • GENBANK/FJ477896