Neuron-Specific Expression of Tomosyn1 in the Mouse Hippocampal Dentate Gyrus Impairs Spatial Learning and Memory
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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.
KeywordsSynaptic plasticity Synaptic transmission Behavior Tomosyn Short-term plasticity Hippocampus Lentivirus Dentate gyrus
- D’Adamo, P., Wolfer, D. P., et al. (2004). Mice deficient for the synaptic vesicle protein Rab3a show impaired spatial reversal learning and increased explorative activity but none of the behavioral changes shown by mice deficient for the Rab3a regulator Gdi1. The European Journal of Neuroscience, 19(7), 1895–1905.PubMedCrossRefGoogle Scholar
- Naldini, L., Blomer, U., et al. (1996). Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proceedings of the National Academy of Sciences of the United States of America, 93(21), 11382–11388.PubMedCrossRefGoogle Scholar
- Yamamoto, Y., Fujikura, K., et al. (2010). The tail domain of tomosyn controls membrane fusion through tomosyn displacement by VAMP2. Biochemical and Biophysical Research Communications 399(1): 24–30.Google Scholar