NeuroMolecular Medicine

, Volume 15, Issue 2, pp 351–363 | Cite as

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

  • Boaz Barak
  • Eitan Okun
  • Yoav Ben-Simon
  • Ayal Lavi
  • Ronit Shapira
  • Ravit Madar
  • Yue Wang
  • Eric Norman
  • Anton Sheinin
  • Mario A. Pita
  • Ofer Yizhar
  • Mohamed R. Mughal
  • Edward Stuenkel
  • Henriette van Praag
  • Mark P. Mattson
  • Uri Ashery
Original Paper

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 

Supplementary material

12017_2013_8223_MOESM1_ESM.doc (3.6 mb)
Supplementary material 1 (DOC 3650 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Boaz Barak
    • 1
    • 2
  • Eitan Okun
    • 3
    • 4
  • Yoav Ben-Simon
    • 1
    • 2
  • Ayal Lavi
    • 1
    • 2
  • Ronit Shapira
    • 1
  • Ravit Madar
    • 3
    • 4
  • Yue Wang
    • 5
  • Eric Norman
    • 5
  • Anton Sheinin
    • 1
  • Mario A. Pita
    • 5
  • Ofer Yizhar
    • 7
  • Mohamed R. Mughal
    • 5
  • Edward Stuenkel
    • 6
  • Henriette van Praag
    • 5
  • Mark P. Mattson
    • 5
  • Uri Ashery
    • 1
    • 2
  1. 1.Department of Neurobiology, Life Sciences FacultyTel Aviv UniversityTel AvivIsrael
  2. 2.Sagol School of NeuroscienceTel Aviv UniversityTel AvivIsrael
  3. 3.The Mina and Everard Goodman Faculty of Life SciencesBar Ilan UniversityRamat-GanIsrael
  4. 4.The Gonda (Goldschmidt) Multidisciplinary Brain Research CenterBar Ilan UniversityRamat-GanIsrael
  5. 5.Laboratory of NeurosciencesNational Institute On Aging Intramural Research Program, NIHBaltimoreUSA
  6. 6.Department of Molecular and Integrative PhysiologyUniversity of MichiganAnn ArborUSA
  7. 7.Department of NeurobiologyWeizmann Institute of ScienceRehovotIsrael

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