5-HT3A receptors are required in long-term depression and AMPA receptor internalization

Y Yu; D-Q Cao; H-Y Xu; M Sun; Z-L Huang; W-H Yung; N Lu; Y Huang

doi:10.1016/j.neuroscience.2014.07.070

5-HT3A receptors are required in long-term depression and AMPA receptor internalization

Neuroscience. 2014 Oct 10:278:105-12. doi: 10.1016/j.neuroscience.2014.07.070. Epub 2014 Aug 15.

Authors

Y Yu¹, D-Q Cao¹, H-Y Xu¹, M Sun², Z-L Huang³, W-H Yung⁴, N Lu⁵, Y Huang⁶

Affiliations

¹ Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
² R&D China, GlaxoSmithKline, Pudong, Shanghai 201203, China.
³ Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai, China.
⁴ School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
⁵ Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: [email protected].
⁶ Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: [email protected].

PMID: 25130560
DOI: 10.1016/j.neuroscience.2014.07.070

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.

Keywords: 5-HT(3A) receptor; AMPA receptor internalization; dendritic spines; long-term depression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CA1 Region, Hippocampal / physiology*
Long-Term Synaptic Depression*
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Transport
Pyramidal Cells / physiology
Receptors, AMPA / metabolism*
Receptors, Metabotropic Glutamate / physiology
Receptors, N-Methyl-D-Aspartate / physiology*
Receptors, Serotonin, 5-HT3 / genetics
Receptors, Serotonin, 5-HT3 / physiology*
Serotonin / analysis

Substances

Receptors, AMPA
Receptors, Metabotropic Glutamate
Receptors, N-Methyl-D-Aspartate
Receptors, Serotonin, 5-HT3
Serotonin