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

Yong Seok Lee, Sun Lim Choi, Seung Hee Lee, Hyoung Kim, Hyungju Park, Nuribalhae Lee, Sue Hyun Lee, Yeon Su Chae, Deok Jin Jang, Eric R. Kandel, Bong Kiun Kaang

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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-HTapAC1, stimulates the production of cAMP in HEK293T cells and in Xenopus oocytes. Moreover, the knockdown of 5-HTapAC1 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-HTapAC1 as a major modulator of learning related synaptic facilitation in the direct sensory to motor neuron pathway of the gill withdrawal reflex.

Original languageEnglish
Pages (from-to)14634-14639
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number34
StatePublished - 25 Aug 2009


  • 5-HT receptor
  • Memory
  • Protein kinase A
  • cAMP

Cite this