期刊
JOURNAL OF NEUROCHEMISTRY
卷 136, 期 1, 页码 36-47出版社
WILEY
DOI: 10.1111/jnc.13379
关键词
active zone; associative learning; hippocampus; mouse; pre-synaptic; short-term plasticity
资金
- Japan Society for the Promotion of Science
- Ministry of Education, Science, Sports, Culture and Technology of Japan
- Japan Science and Technology Agency, PRESTO
- [26115523]
- Grants-in-Aid for Scientific Research [25293136, 25430015, 16K07004, 15H01295, 26115523] Funding Source: KAKEN
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 invivo 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.
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