title: Left-right asymmetry defect in the hippocampal circuitry impairs spatial learning and working memory in iv mice.
abstract: Although left-right (L-R) asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B) subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv) mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness) in the synaptic distribution of the ε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP) task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L-R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory.
authors.affiliation: Japan Society for the Promotion of Science, Tokyo, Japan. kgoto@psy.flet.keio.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Goto
authors.forename: Ryo
authors.initials: R
authors.lastname: Kurashima
authors.forename: Hayato
authors.initials: H
authors.lastname: Gokan
authors.forename: Naomi
authors.initials: N
authors.lastname: Inoue
authors.forename: Isao
authors.initials: I
authors.lastname: Ito
authors.forename: Shigeru
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000465:Algorithms; D000818:Animals; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology; D012857:Situs Inversus / Q000235:genetics / Q000503:physiopathology*; D013028:Space Perception / Q000502:physiology
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate