1. Altered presynaptic function and number of mitochondria in the medial prefrontal cortex of adult Cyfip2 heterozygous mice.
- Author
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Kim GH, Zhang Y, Kang HR, Lee SH, Shin J, Lee CH, Kang H, Ma R, Jin C, Kim Y, Kim SY, Kwon SK, Choi SY, Lee KJ, and Han K
- Subjects
- Animals, Heterozygote, Mice, Mitochondria ultrastructure, Prefrontal Cortex ultrastructure, Presynaptic Terminals ultrastructure, Adaptor Proteins, Signal Transducing metabolism, Mitochondria metabolism, Prefrontal Cortex metabolism, Presynaptic Terminals metabolism
- 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.- Published
- 2020
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