Identification of a serotonin receptor coupled to adenylyl cyclase involved in learning-related heterosynaptic facilitation in Aplysia |
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| Authors: | 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 |
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| Institution: | aNational Creative Research Initiative Center for Memory and Institute of Molecular Biology and Genetics, Departments of Biological Sciences and ;cBrain and Cognitive Sciences, College of Natural Sciences, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151–747, Korea; and ;bCenter for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, New York, NY 10032 |
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| Abstract: | 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. |
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| Keywords: | 5-HT receptor memory cAMP protein kinase A |
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