title: Colocalisation of serotonin2A receptors with the glutamate receptor subunits NR1 and GluR2 in the dentate gyrus: an ultrastructural study of a modulatory role.
abstract: The serotonin(2A) receptor (5-HT(2A)R) is implicated in many neurological disorders and has a role in cognitive processes, reliant upon hippocampal glutamate receptors. Recent studies show that 5-HT(2A)R agonists and/or antagonists can influence cognitive function, suggesting a critical hippocampal role for these receptors, yet their cellular and subcellular distribution within this region has not been comprehensively analysed. Here, we have conducted an electron microscopic examination of 5-HT(2A)R distribution with the glutamate N-methyl-D-aspartate (NMDA) and amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor subunits NR1 and GluR2 in the hippocampal dentate gyrus (DG) in order to investigate whether 5-HT(2A)R location is compatible with a modulatory role over NMDA and/or AMPA receptor mediated neurotransmission. Of 5-HT(2A)R positive profiles, 56% were dendrites and 16% were dendritic spines. Labelling was both cytoplasmic and membranous. Spinous labelling was more frequently membranous at peri- and extra-synaptic sites, though was also associated with synaptic specialisations. Profiles displaying colocalisation of immunoreactivity for 5-HT(2A)Rs with NR1 or GluR2 were predominantly dendrites, representing 11% and 8% of 5-HT(2A)R positive profiles, respectively. Additionally, 12% of 5-HT(2A)R labelled profiles also displayed immunoreactivity for gamma-aminobutyric acid (GABA). These data indicate most 5-HT(2A)Rs are expressed on granule cell projections, with a smaller subpopulation expressed on GABAergic interneurons.
authors.affiliation: Department of Life Sciences, The Open University, Milton Keynes, MK7 6AA, UK. cjpeddie@aol.com
authors.forename: C J
authors.initials: CJ
authors.lastname: Peddie
authors.forename: H A
authors.initials: HA
authors.lastname: Davies
authors.forename: F M
authors.initials: FM
authors.lastname: Colyer
authors.forename: M G
authors.initials: MG
authors.lastname: Stewart
authors.forename: J J
authors.initials: JJ
authors.lastname: Rodríguez
mesh_terms: D000818:Animals; D003712:Dendrites / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D021122:Protein Subunits / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000096:biosynthesis / Q000378:metabolism* / Q000648:ultrastructure*; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000378:metabolism* / Q000648:ultrastructure*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000378:metabolism* / Q000648:ultrastructure*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: C409466:NR1 NMDA receptor; D021122:Protein Subunits; D044402:Receptor, Serotonin, 5-HT2A; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C104722:glutamate receptor ionotropic, AMPA 2