title: Cognitive Deficits in Calsyntenin-2-deficient Mice Associated with Reduced GABAergic Transmission.
abstract: Calsyntenin-2 has an evolutionarily conserved role in cognition. In a human genome-wide screen, the CLSTN2 locus was associated with verbal episodic memory, and expression of human calsyntenin-2 rescues the associative learning defect in orthologous Caenorhabditis elegans mutants. Other calsyntenins promote synapse development, calsyntenin-1 selectively of excitatory synapses and calsyntenin-3 of excitatory and inhibitory synapses. We found that targeted deletion of calsyntenin-2 in mice results in a selective reduction in functional inhibitory synapses. Reduced inhibitory transmission was associated with a selective reduction of parvalbumin interneurons in hippocampus and cortex. Clstn2(-/-) mice showed normal behavior in elevated plus maze, forced swim test, and novel object recognition assays. However, Clstn2(-/-) mice were hyperactive in the open field and showed deficits in spatial learning and memory in the Morris water maze and Barnes maze. These results confirm a function for calsyntenin-2 in cognitive performance and indicate an underlying mechanism that involves parvalbumin interneurons and aberrant inhibitory transmission.
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.|Federal State Budgetary Scientific Institution, Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Lipina
authors.affiliation: Brain Research Centre and Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Tuhina
authors.initials: T
authors.lastname: Prasad
authors.affiliation: Brain Research Centre and Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Yokomaku
authors.affiliation: Brain Research Centre and Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Lin
authors.initials: L
authors.lastname: Luo
authors.affiliation: Brain Research Centre and Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.|Brain Research Centre and Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Connor
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, Göttingen, Germany.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawabe
authors.affiliation: Brain Research Centre and Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Yu Tian
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, Göttingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: John C
authors.initials: JC
authors.lastname: Roder
authors.affiliation: Brain Research Centre and Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Craig
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D003072:Cognition Disorders / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D010320:Parvalbumins / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D010320:Parvalbumins; C472552:calsyntenin-2, mouse; D005680:gamma-Aminobutyric Acid