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Publication : SCRAPPER Selectively Contributes to Spontaneous Release and Presynaptic Long-Term Potentiation in the Anterior Cingulate Cortex.

First Author  Koga K Year  2017
Journal  J Neurosci Volume  37
Issue  14 Pages  3887-3895
PubMed ID  28292828 Mgi Jnum  J:240596
Mgi Id  MGI:5888783 Doi  10.1523/JNEUROSCI.0023-16.2017
Citation  Koga K, et al. (2017) SCRAPPER Selectively Contributes to Spontaneous Release and Presynaptic Long-Term Potentiation in the Anterior Cingulate Cortex. J Neurosci 37(14):3887-3895
abstractText  SCRAPPER is an E3 ubiquitin ligase expressed in presynaptic terminals, neural cell body, and dendrites of the hippocampus and cortex, which is coded by the FBXL20 gene. 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 STATEMENT The 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.
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