title: Hippocampal 5-HT7 receptors signal phosphorylation of the GluA1 subunit to facilitate AMPA receptor mediated-neurotransmission in vitro and in vivo.
abstract: OBJECTIVE
  The 5-HT7 receptor is a GPCR that is the target of a broad range of antidepressant and antipsychotic drugs. Various studies have demonstrated an ability of the 5-HT7 receptor to modulate glutamatergic neurotransmission and cognitive processes although the potential impact upon AMPA receptors has not been investigated directly. The purposes of the present study were to investigate a direct modulation of the GluA1 AMPA receptor subunit and determine how this might influence AMPA receptor function.
  
  
  METHODS
  The influence of pharmacological manipulation of the 5-HT7 receptor system upon phosphorylation of GluA1 subunits was assessed by Western blotting of fractionated proteins from hippocampal neurones in culture (or proteins resident at the neurone surface) and the functional impact assessed by electrophysiological recordings in rat hippocampus in vitro and in vivo.
  
  
  RESULTS
  5-HT7 receptor activation increased cAMP and relative pCREB levels in cultures of rat hippocampal neurones along with an increase in phosphorylation (Ser845) of the GluA1 AMPA receptor subunit evident in whole neurone extracts and within the neurone surface compartment. Electrophysiological recordings in rat hippocampus demonstrated a 5-HT7 receptor-mediated increase in AMPA receptor-mediated neurotransmission in vitro and in vivo.
  
  
  CONCLUSIONS
  The 5-HT7 receptor-mediated phosphorylation of the GluA1 AMPA receptor provides a molecular mechanism consistent with the 5-HT7 receptor-mediated increase in AMPA receptor-mediated neurotransmission.
authors.affiliation: Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.|Neurosciences CEDD, GlaxoSmithKline Medicine Research Centre, Verona, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Andreetta
authors.affiliation: Neurosciences CEDD, GlaxoSmithKline Medicine Research Centre, Verona, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Carboni
authors.affiliation: Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Grafton
authors.affiliation: NeuroSolutions Limited, Coventry, UK.
authors.forename: Ross
authors.initials: R
authors.lastname: Jeggo
authors.affiliation: NeuroSolutions Limited, Coventry, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Whyment
authors.affiliation: NeuroSolutions Limited, Coventry, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: van den Top
authors.affiliation: Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Vic., Australia.|The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, Victoria 3052, Australia.|Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoyer
authors.affiliation: NeuroSolutions Limited, Coventry, UK.
authors.forename: David
authors.initials: D
authors.lastname: Spanswick
authors.affiliation: Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.|Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Barnes
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D010766:Phosphorylation; D021122:Protein Subunits / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry* / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor