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Altered presynaptic function and number of mitochondria in the medial prefrontal cortex of adult Cyfip2 heterozygous mice

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Authors
Kim, Gyu Hyun; Zhang, Yinhua; Kang, Hyae Rim; Lee, Seung-Hyun; Shin, Jiwon; Lee, Chan Hee; Kang, Hyojin; Ma, Ruiying; Jin, Chunmei; Kim, Yoonhee; Kim, Su Yeon; Kwon, Seok-Kyu; Choi, Se-Young; Lee, Kea Joo; Han, Kihoon
Issue Date
2020-09-11
Publisher
BMC
Citation
Molecular Brain, 13(1):123
Keywords
PresynapseMitochondriaMedial prefrontal cortexCytoplasmic FMR1-interacting protein 2
Abstract
Variants of the cytoplasmic FMR1-interacting protein (CYFIP) gene family, CYFIP1 and CYFIP2, are associated with numerous neurodevelopmental and neuropsychiatric disorders. According to several studies, CYFIP1 regulates the development and function of both pre- and post-synapses in neurons. Furthermore, various studies have evaluated CYFIP2 functions in the postsynaptic compartment, such as regulating dendritic spine morphology; however, no study has evaluated whether and how CYFIP2 affects presynaptic functions. To address this issue, in this study, we have focused on the presynapses of layer 5 neurons of the medial prefrontal cortex (mPFC) in adult Cyfip2 heterozygous (Cyfip2+/−) mice. Electrophysiological analyses revealed an enhancement in the presynaptic short-term plasticity induced by high-frequency stimuli in Cyfip2+/− neurons compared with wild-type neurons. Since presynaptic mitochondria play an important role in buffering presynaptic Ca2+, which is directly associated with the short-term plasticity, we analyzed presynaptic mitochondria using electron microscopic images of the mPFC. Compared with wild-type mice, the number, but not the volume or cristae density, of mitochondria in both presynaptic boutons and axonal processes in the mPFC layer 5 of Cyfip2+/− mice was reduced. Consistent with an identification of mitochondrial proteins in a previously established CYFIP2 interactome, CYFIP2 was detected in a biochemically enriched mitochondrial fraction of the mouse mPFC. Collectively, these results suggest roles for CYFIP2 in regulating presynaptic functions, which may involve presynaptic mitochondrial changes.
ISSN
1756-6606
Language
English
URI
http://hdl.handle.net/10371/168949
DOI
https://doi.org/10.1186/s13041-020-00668-4
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dental Research Institute (치학연구소)Journal Papers (저널논문_치학연구소)
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