title: 5-HT3A receptors are required in long-term depression and AMPA receptor internalization.
abstract: 5-Hydroxytrytamine (serotonin) type 3A receptors (5-HT3ARs), as the only ligand-gated ion channels in the serotonin receptor family, are known to regulate neuronal excitation and release of GABA in hippocampal interneurons. However, their physiological role in glutamatergic synaptic plasticity remains unclear. Here, we show that deletion of the 5-HT3AR gene in transgenic mice abolished N-methyl-d-aspartate (NMDA) receptor (NMDAR)-dependent long-term depression (LTD) induced by low-frequency stimulation (LFS) in hippocampal CA1 synapses in slices, whereas the metabotropic glutamate receptor (mGluR)-dependent LTD did not change in the 5-HT3AR knockout mice. In addition, 5-HT3ARs disruption inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) internalization, without altering basal surface levels of AMPARs. However, the deletion of 5-HT3ARs did not lead to loss of synapses and structural alteration of dendritic spines. Furthermore, the concentrations of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus were not affected by the deletion of 5-HT3ARs. These observations revealed an important role of 5-HT3ARs in NMDAR-dependent long-term depression, which is critical for learning behaviors.
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: D-Q
authors.initials: DQ
authors.lastname: Cao
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Xu
authors.affiliation: R&D China, GlaxoSmithKline, Pudong, Shanghai 201203, China.
authors.forename: M
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Z-L
authors.initials: ZL
authors.lastname: Huang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: W-H
authors.initials: WH
authors.lastname: Yung
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: luning7@shmu.edu.cn.
authors.forename: N
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: yinghuang@shmu.edu.cn.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D036881:Long-Term Synaptic Depression; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021381:Protein Transport; D017966:Pyramidal Cells / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000032:analysis
chemical_list: D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin
keywords: 5-HT(3A) receptor; AMPA receptor internalization; dendritic spines; long-term depression