title: SCRAPPER Selectively Contributes to Spontaneous Release and Presynaptic Long-Term Potentiation in the Anterior Cingulate Cortex.
abstract: SCRAPPER is an E3 ubiquitin ligase expressed in presynaptic terminals, neural cell body, and dendrites of the hippocampus and cortex, which is coded by theFBXL20gene. SCRAPPER is known to regulate synaptic transmissions and long-term potentiation (LTP) in the hippocampus, but no report is available for the cortex. Here we show genetic evidence for critical roles of SCRAPPER in excitatory transmission and presynaptic LTP (pre-LTP) of the anterior cingulate cortex (ACC), a critical cortical region for pain, anxiety, and fear. Miniature and spontaneous releases, but not evoked release, of glutamate were significantly increased in SCRAPPER knock-out (SCR-KO) mice. Interestingly, SCRAPPER selectively contributes to the increases of frequency and amplitude. The pre-LTP in the ACC was completely blocked in SCR-KO mice. Our results thus provide direct evidence for SCRAPPER in both spontaneous release and pre-LTP in the ACC and reveal a potential novel target for treating anxiety-related disease.SIGNIFICANCE STATEMENTThe anterior cingulate cortex (ACC) plays critical roles in pain, anxiety, and fear. Peripheral injury induces long-term changes in synaptic transmission in the ACC. Our recent study found that a presynaptic form of LTP (pre-LTP) in the ACC contributes to chronic pain-induced anxiety. Here, we show that SCRAPPER plays a critical role in ACC pre-LTP as well as synaptic transmission.
authors.affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.|Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.|Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Koga
authors.affiliation: Department of Optical Imaging, Institute for Medical Photonics Research, and.|International Mass Imaging Center, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yao
authors.affiliation: International Mass Imaging Center, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.|Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.|Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|Division of Neural Systematics, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi, 4440867, Japan, and.|Riken Center for Molecular Imaging Science, Kobe, Hyogo 6500047, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China, min.zhuo@utoronto.ca.|Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D044783:F-Box Proteins; D018698:Glutamic Acid / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000172:deficiency* / Q000235:genetics
chemical_list: D044783:F-Box Proteins; C523476:Fbxl20 protein, mouse; D009419:Nerve Tissue Proteins; D018698:Glutamic Acid; D043743:Ubiquitin-Protein Ligase Complexes
keywords: LTP; cortex; knock-out mice; presynaptic; scrapper; spontaneous release