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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)351-363
Number of pages13
JournalNeuroMolecular Medicine
Volume15
Issue number2
DOIs
StatePublished - Jun 2013

Keywords

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

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