title: 5-HT3a Receptors Modulate Hippocampal Gamma Oscillations by Regulating Synchrony of Parvalbumin-Positive Interneurons.
abstract: Gamma-frequency oscillatory activity plays an important role in information integration across brain areas. Disruption in gamma oscillations is implicated in cognitive impairments in psychiatric disorders, and 5-HT3 receptors (5-HT3Rs) are suggested as therapeutic targets for cognitive dysfunction in psychiatric disorders. Using a 5-HT3aR-EGFP transgenic mouse line and inducing gamma oscillations by carbachol in hippocampal slices, we show that activation of 5-HT3aRs, which are exclusively expressed in cholecystokinin (CCK)-containing interneurons, selectively suppressed and desynchronized firings in these interneurons by enhancing spike-frequency accommodation in a small conductance potassium (SK)-channel-dependent manner. Parvalbumin-positive interneurons therefore received diminished inhibitory input leading to increased but desynchronized firings of PV cells. As a consequence, the firing of pyramidal neurons was desynchronized and gamma oscillations were impaired. These effects were independent of 5-HT3aR-mediated CCK release. Our results therefore revealed an important role of 5-HT3aRs in gamma oscillations and identified a novel crosstalk among different types of interneurons for regulation of network oscillations. The functional link between 5-HT3aR and gamma oscillations may have implications for understanding the cognitive impairments in psychiatric disorders.
authors.affiliation: Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Maryland 20892, USA Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Maryland 20892, USA.
authors.forename: Kristopher
authors.initials: K
authors.lastname: Yoon
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Ho
authors.initials: H
authors.lastname: Ko
authors.affiliation: Gene, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Maryland 20892, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Jiao
authors.affiliation: Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Maryland 20892, USA Virginia Tech Carilion Research Institute, Roanoke, VA 24016, USA.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ito
authors.affiliation: Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Jian-Young
authors.initials: JY
authors.lastname: Wu
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Wing-Ho
authors.initials: WH
authors.lastname: Yung
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Bai
authors.initials: B
authors.lastname: Lu
authors.affiliation: Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Maryland 20892, USA Virginia Tech Carilion Research Institute, Roanoke, VA 24016, USA.
authors.forename: Alexei
authors.initials: A
authors.lastname: Morozov
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D065818:Gamma Rhythm / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D006727:Hormone Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010320:Parvalbumins / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D054830:Sesterterpenes; D013057:Spectrum Analysis
chemical_list: D001030:Apamin; D001569:Benzodiazepines; D002217:Carbachol; D018679:Cholinergic Agonists; D058787:GABA-A Receptor Antagonists; D006727:Hormone Antagonists; D010320:Parvalbumins; D010852:Picrotoxin; D044406:Receptors, Serotonin, 5-HT3; D018490:Serotonin Agents; D054830:Sesterterpenes; C087260:YM 022; C022961:picrotoxinin
keywords: 5-HT3a receptors; CCK interneurons; PV interneurons; gamma oscillations; hippocampus