title: Neuron-specific expression of tomosyn1 in the mouse hippocampal dentate gyrus impairs spatial learning and memory.
abstract: Tomosyn, a syntaxin-binding protein, is known to inhibit vesicle priming and synaptic transmission via interference with the formation of SNARE complexes. Using a lentiviral vector, we specifically overexpressed tomosyn1 in hippocampal dentate gyrus neurons in adult mice. Mice were then subjected to spatial learning and memory tasks and electrophysiological measurements from hippocampal slices. Tomosyn1-overexpression significantly impaired hippocampus-dependent spatial memory while tested in the Morris water maze. Further, tomosyn1-overexpressing mice utilize swimming strategies of lesser cognitive ability in the Morris water maze compared with control mice. Electrophysiological measurements at mossy fiber-CA3 synapses revealed impaired paired-pulse facilitation in the mossy fiber of tomosyn1-overexpressing mice. This study provides evidence for novel roles for tomosyn1 in hippocampus-dependent spatial learning and memory, potentially via decreased synaptic transmission in mossy fiber-CA3 synapses. Moreover, it provides new insight regarding the role of the hippocampal dentate gyrus and mossy fiber-CA3 synapses in swimming strategy preference, and in learning and memory.
authors.affiliation: Department of Neurobiology, Life Sciences Faculty, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Boaz
authors.initials: B
authors.lastname: Barak
authors.forename: Eitan
authors.initials: E
authors.lastname: Okun
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Simon
authors.forename: Ayal
authors.initials: A
authors.lastname: Lavi
authors.forename: Ronit
authors.initials: R
authors.lastname: Shapira
authors.forename: Ravit
authors.initials: R
authors.lastname: Madar
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Eric
authors.initials: E
authors.lastname: Norman
authors.forename: Anton
authors.initials: A
authors.lastname: Sheinin
authors.forename: Mario A
authors.initials: MA
authors.lastname: Pita
authors.forename: Ofer
authors.initials: O
authors.lastname: Yizhar
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Mughal
authors.forename: Edward
authors.initials: E
authors.lastname: Stuenkel
authors.forename: Henriette
authors.initials: H
authors.lastname: van Praag
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Uri
authors.initials: U
authors.lastname: Ashery
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D056654:CA3 Region, Hippocampal / Q000378:metabolism / Q000503:physiopathology*; D018891:Dentate Gyrus / Q000378:metabolism / Q000503:physiopathology*; D005106:Exploratory Behavior / Q000502:physiology; D017930:Genes, Reporter; D005822:Genetic Vectors; D007859:Learning Disabilities / Q000235:genetics* / Q000503:physiopathology; D016086:Lentivirus; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019599:Mossy Fibers, Hippocampal / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D050683:R-SNARE Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013550:Swimming; D015854:Up-Regulation
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D011993:Recombinant Fusion Proteins; C484769:Stxbp5 protein, rat; C112618:tomosyn protein, mouse; C054562:yellow fluorescent protein, Bacteria