title: SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.
abstract: Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain. We found that the paired-pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD-B KO mice compared with wild-type littermates. We also found that the frequency of the miniature excitatory post-synaptic current was decreased in SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency synaptic stimulation was significantly enhanced in SAD-B KO mice. These results suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice. These observations suggest that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre-synaptic terminals, that SAD-B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain.
authors.affiliation: Department of Neuroscience, School of Medicine, Jikei University, Tokyo, Japan.|Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Kawaguchi, Saitama, Japan.
authors.forename: Ayako M
authors.initials: AM
authors.lastname: Watabe
authors.affiliation: Department of Neuroscience, School of Medicine, Jikei University, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Nagase
authors.affiliation: Department of Biochemistry, University of Yamanashi, Yamanashi, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Hagiwara
authors.affiliation: Department of Biochemistry, University of Yamanashi, Yamanashi, Japan.
authors.forename: Yamato
authors.initials: Y
authors.lastname: Hida
authors.affiliation: Department of Neuroscience, School of Medicine, Jikei University, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Neuroscience, School of Medicine, Jikei University, Tokyo, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Ochiai
authors.affiliation: Department of Neuroscience, School of Medicine, Jikei University, Tokyo, Japan.
authors.forename: Fusao
authors.initials: F
authors.lastname: Kato
authors.affiliation: Department of Biochemistry, University of Yamanashi, Yamanashi, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ohtsuka
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005239:Fear / Q000502:physiology* / Q000523:psychology; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000502:physiology*; D013569:Synapses; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: C496826:Brsk1 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: active zone; associative learning; hippocampus; mouse; pre-synaptic; short-term plasticity