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.
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Acknowledgments We would like to thank Prof. Pablo Castillo for comments on the manuscript, Dr. Peisu Zhang for technical help, and Dr. Sarah Rothman for editing the manuscript. This research was supported, in part, by the Intramural Research Program of the National Institute on Aging, NIH, the Israel Science Foundation (Grant no. 1211/07 and 730/11; U.A.) and the BSF (Grant no. 2009279; U.A.), the National Institutes of Health (RO1 NS053978; E.S. and U.A.) and by travel grant from Boehringer Ingelheim Fonds (awarded to Boaz Barak).
- Dentate gyrus
- Short-term plasticity
- Synaptic plasticity
- Synaptic transmission