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SAD‐B kinase regulates pre‐synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory
Author(s) -
Watabe Ayako M.,
Nagase Masashi,
Hagiwara Akari,
Hida Yamato,
Tsuji Megumi,
Ochiai Toshitaka,
Kato Fusao,
Ohtsuka Toshihisa
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13379
Subject(s) - schaffer collateral , synaptic vesicle , neuroscience , synaptic plasticity , biology , neurotransmission , hippocampal formation , synaptic fatigue , synapse , excitatory postsynaptic potential , synaptic augmentation , hippocampus , neural facilitation , microbiology and biotechnology , inhibitory postsynaptic potential , vesicle , biochemistry , receptor , membrane
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.