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

doi:10.1007/s12017-013-8223-4

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

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14 Scopus citations

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 language	English
Pages (from-to)	351-363
Number of pages	13
Journal	NeuroMolecular Medicine
Volume	15
Issue number	2
DOIs	https://doi.org/10.1007/s12017-013-8223-4
State	Published - Jun 2013

Bibliographical note

Funding Information:
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).

Keywords

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

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10.1007/s12017-013-8223-4

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Barak, B., Okun, E., Ben-Simon, Y., Lavi, A., Shapira, R., Madar, R., Wang, Y., Norman, E., Sheinin, A., Pita, M. A., Yizhar, O., Mughal, M. R., Stuenkel, E., Van Praag, H., Mattson, M. P., & Ashery, U. (2013). Neuron-specific expression of tomosyn1 in the mouse hippocampal dentate gyrus impairs spatial learning and memory. NeuroMolecular Medicine, 15(2), 351-363. https://doi.org/10.1007/s12017-013-8223-4

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title = "Neuron-specific expression of tomosyn1 in the mouse hippocampal dentate gyrus impairs spatial learning and memory",

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

author = "Boaz Barak and Eitan Okun and Yoav Ben-Simon and Ayal Lavi and Ronit Shapira and Ravit Madar and Yue Wang and Eric Norman and Anton Sheinin and Pita, {Mario A.} and Ofer Yizhar and Mughal, {Mohamed R.} and Edward Stuenkel and {Van Praag}, Henriette and Mattson, {Mark P.} and Uri Ashery",

note = "Funding Information: 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).",

year = "2013",

month = jun,

doi = "10.1007/s12017-013-8223-4",

language = "אנגלית",

volume = "15",

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journal = "NeuroMolecular Medicine",

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Barak, B, Okun, E, Ben-Simon, Y, Lavi, A, Shapira, R, Madar, R, Wang, Y, Norman, E, Sheinin, A, Pita, MA, Yizhar, O, Mughal, MR, Stuenkel, E, Van Praag, H, Mattson, MP & Ashery, U 2013, 'Neuron-specific expression of tomosyn1 in the mouse hippocampal dentate gyrus impairs spatial learning and memory', NeuroMolecular Medicine, vol. 15, no. 2, pp. 351-363. https://doi.org/10.1007/s12017-013-8223-4

TY - JOUR

T1 - Neuron-specific expression of tomosyn1 in the mouse hippocampal dentate gyrus impairs spatial learning and memory

AU - Barak, Boaz

AU - Okun, Eitan

AU - Ben-Simon, Yoav

AU - Lavi, Ayal

AU - Shapira, Ronit

AU - Madar, Ravit

AU - Wang, Yue

AU - Norman, Eric

AU - Sheinin, Anton

AU - Pita, Mario A.

AU - Yizhar, Ofer

AU - Mughal, Mohamed R.

AU - Stuenkel, Edward

AU - Van Praag, Henriette

AU - Mattson, Mark P.

AU - Ashery, Uri

N1 - Funding Information: 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).

PY - 2013/6

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N2 - 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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KW - Hippocampus

KW - Lentivirus

KW - Short-term plasticity

KW - Synaptic plasticity

KW - Synaptic transmission

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Neuron-specific expression of tomosyn1 in the mouse hippocampal dentate gyrus impairs spatial learning and memory

Abstract

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Keywords

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