title: The 5-HT7 receptor is involved in allocentric spatial memory information processing.
abstract: The hippocampus has been implicated in aspects of spatial memory. Its ability to generate new neurons has been suggested to play a role in memory formation. Hippocampal serotonin (5-HT) neurotransmission has also been proposed as a contributor to memory processing. Studies have shown that the 5-HT(7) receptor is present in the hippocampus in relatively high abundance. Thus the aim of the present study was to investigate the possible role of the 5-HT(7) receptor in spatial memory using 5-HT(7) receptor-deficient mice (5-HT(7)(-/-)). A hippocampus-associated spatial memory deficit in 5-HT(7)(-/-) mice was demonstrated using a novel location/novel object test. A similar reduction in novel location exploration was observed in C57BL/6J mice treated with the selective 5-HT(7) receptor antagonist SB-269970. These findings prompted an extended analysis using the Barnes maze demonstrating that 5-HT(7)(-/-) mice were less efficient in accommodating to changes in spatial arrangement than 5-HT(7)(+/+) mice. 5-HT(7)(-/-) mice had specific impairments in memory compilation required for resolving spatial tasks, which resulted in impaired allocentric spatial memory whereas egocentric spatial memory remained intact after the mice were forced to switch back from striatum-dependent egocentric to hippocampus-dependent allocentric memory. To further investigate the physiological bases underlining these behaviors we compared hippocampal neurogenesis in 5-HT(7)(+/+) and 5-HT(7)(-/-) mice employing BrdU immunohistochemistry. The rate of cell proliferation in the dentate gyrus was identical in the two genotypes. From the current data we conclude that the 5-HT(7)(-/-) mice performed by remembering a simple sequence of actions that resulted in successfully locating a hidden target in a static environment.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Gor
authors.initials: G
authors.lastname: Sarkisyan
authors.forename: Peter B
authors.initials: PB
authors.lastname: Hedlund
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology; D010636:Phenols / Q000008:administration & dosage; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000008:administration & dosage; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D001973:Bromodeoxyuridine