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Altered presynaptic function and number of mitochondria in the medial prefrontal cortex of adultCyfip2heterozygous mice

Authors
Kim, Gyu HyunZhang, YinhuaKang, Hyae RimLee, Seung-HyunShin, JiwonLee, Chan HeeKang, HyojinMa, RuiyingJin, ChunmeiKim, YoonheeKim, Su YeonKwon, Seok-KyuChoi, Se-YoungLee, Kea JooHan, Kihoon
Issue Date
11-9월-2020
Publisher
BMC
Keywords
Presynapse; Mitochondria; Medial prefrontal cortex; Cytoplasmic FMR1-interacting protein 2
Citation
MOLECULAR BRAIN, v.13, no.1
Indexed
SCIE
SCOPUS
Journal Title
MOLECULAR BRAIN
Volume
13
Number
1
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/53170
DOI
10.1186/s13041-020-00668-4
ISSN
1756-6606
Abstract
Variants of the cytoplasmic FMR1-interacting protein (CYFIP) gene family,CYFIP1andCYFIP2, 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 adultCyfip2heterozygous (Cyfip2(+/-)) mice. Electrophysiological analyses revealed an enhancement in the presynaptic short-term plasticity induced by high-frequency stimuli inCyfip2(+/-)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 ofCyfip2(+/-)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.
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