title: Contextual fear conditioning modulates hippocampal AMPA-, GluN1- and serotonin receptor 5-HT1A-containing receptor complexes.
abstract: Although the roles of AMPAR (α-amino-3-hydroxyl-5-methyl-4-isoxazole propionate receptor), NMDAR (N-methyl-D-aspartate receptor) and 5HT1AR (5-hydroxytryptamine sub type 1A) in contextual fear conditioning (cFC) have been studied, information about receptor-containing complexes (RC) is not available. Moreover, there are no data on membrane or endosomal NMDA-, 5HT1A- or AMPA-RC levels, which would likely be indicative of the trafficking of these receptors. cFC was carried out in C57BL/6j mice and animals were sacrificed in the individual phases and hippocampi were taken for the determination of receptor complex and subunit levels using BN- and SDS-PAGE with subsequent Western blotting. GluA1-4, GluN1 (NMDAR subunit NR1)- and 5HT1A-RC were differentially regulated during the individual phases and differentially regulated in the membrane and endosomal fractions. GluA1-RC levels in the membrane were increased in acquisition, consolidation and retrieval phases; GluA2-RC and GluA3-RC membrane levels were reduced and modulated in early endosomes during these phases. GluA4-RC and GluN1-RC levels as well as their subunits showed the same pattern in the membrane during consolidation while 5HT1A-RC membrane and endosome levels were mainly increased during consolidation and retrieval. Taken together, the results suggest that levels of 5-HT1A-RC, NMDA-RC and AMPA-RC and subunits in membrane and endosomal preparations are paralleling individual phases of cFC. The findings from the current study suggest phase-specific receptor complex and subunit formation and propose that receptor complexes should be examined in parallel with receptor subunits to aid the interpretation of previous work and to design future work on neurotransmitter receptors in memory paradigms.
authors.affiliation: Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Sunetra
authors.initials: S
authors.lastname: Sase
authors.affiliation: Institute of Biology, Otto von Guericke University, Magdeburg, 39120 Magdeburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stork
authors.affiliation: Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: gert.lubec@meduniwien.ac.at.
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
authors.affiliation: Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: linli@gmail.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003213:Conditioning, Psychological; D004597:Electroshock / Q000009:adverse effects; D011992:Endosomes / Q000378:metabolism; D005239:Fear; D046352:Freezing Reaction, Cataleptic; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: C121673:Gprin1 protein, mouse; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D044282:Receptor, Serotonin, 5-HT1A
keywords: 5-HT1(A) receptor; AMPA receptor; Contextual fear conditioning; NMDA receptor; Receptor complex