Original Paper

NeuroMolecular Medicine

, Volume 15, Issue 2, pp 351-363

Neuron-Specific Expression of Tomosyn1 in the Mouse Hippocampal Dentate Gyrus Impairs Spatial Learning and Memory

  • Boaz BarakAffiliated withDepartment of Neurobiology, Life Sciences Faculty, Tel Aviv UniversitySagol School of Neuroscience, Tel Aviv University
  • , Eitan OkunAffiliated withThe Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan UniversityThe Gonda (Goldschmidt) Multidisciplinary Brain Research Center, Bar Ilan University
  • , Yoav Ben-SimonAffiliated withDepartment of Neurobiology, Life Sciences Faculty, Tel Aviv UniversitySagol School of Neuroscience, Tel Aviv University
  • , Ayal LaviAffiliated withDepartment of Neurobiology, Life Sciences Faculty, Tel Aviv UniversitySagol School of Neuroscience, Tel Aviv University
  • , Ronit ShapiraAffiliated withDepartment of Neurobiology, Life Sciences Faculty, Tel Aviv University
  • , Ravit MadarAffiliated withThe Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan UniversityThe Gonda (Goldschmidt) Multidisciplinary Brain Research Center, Bar Ilan University
  • , Yue WangAffiliated withLaboratory of Neurosciences, National Institute On Aging Intramural Research Program, NIH
  • , Eric NormanAffiliated withLaboratory of Neurosciences, National Institute On Aging Intramural Research Program, NIH
  • , Anton SheininAffiliated withDepartment of Neurobiology, Life Sciences Faculty, Tel Aviv University
    • , Mario A. PitaAffiliated withLaboratory of Neurosciences, National Institute On Aging Intramural Research Program, NIH
    • , Ofer YizharAffiliated withDepartment of Neurobiology, Weizmann Institute of Science
    • , Mohamed R. MughalAffiliated withLaboratory of Neurosciences, National Institute On Aging Intramural Research Program, NIH
    • , Edward StuenkelAffiliated withDepartment of Molecular and Integrative Physiology, University of Michigan
    • , Henriette van PraagAffiliated withLaboratory of Neurosciences, National Institute On Aging Intramural Research Program, NIH
    • , Mark P. MattsonAffiliated withLaboratory of Neurosciences, National Institute On Aging Intramural Research Program, NIH
    • , Uri AsheryAffiliated withDepartment of Neurobiology, Life Sciences Faculty, Tel Aviv UniversitySagol School of Neuroscience, Tel Aviv University Email author 

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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.

Keywords

Synaptic plasticity Synaptic transmission Behavior Tomosyn Short-term plasticity Hippocampus Lentivirus Dentate gyrus