The Possible Role of Neurobeachin in Extinction of Contextual Fear Memory

Boyoung Lee, Eunyoung Bang, Won Suk Yang, Afshin Paydar, Go Eun Ha, Sujin Kim, Jong Hyun Kim, Taesup Cho, Seung Eun Lee, Sukchan Lee, Myoung Goo Kang, Eunji Cheong, Key Sun Kim, Cheolju Lee, Myeong Hee Yu, Hee Sup Shin

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Abstract

Established fear memory becomes vulnerable to disruption after memory retrieval and extinction; this labile state is critical for inhibiting the return of fear memory. However, the labile state has a very narrow time window after retrieval, and underlying molecular mechanisms are not well known. To that end, we isolated the hippocampus immediately after fear memory retrieval and performed proteomics. We identified Neurobeachin (NBEA), an autism-related regulator of synaptic protein trafficking, to be upregulated after contextual fear memory retrieval. NBEA protein expression was rapid and transient after fear memory retrieval at the synapse. Nbea mRNA was enriched at the synapses, and the rapid induction of NBEA expression was blocked by inhibition of the mammalian target of rapamycin (mTOR)-dependent signaling pathway. Mice with cornu ammonis 1 (CA1)-specific Nbea shRNA knockdown showed normal fear acquisition and contextual fear memory but impaired extinction, suggesting an important role of Nbea in fear memory extinction processes. Consistently, Nbea heterozygotes showed normal fear acquisition and fear memory recall but showed impairment in extinction. Our data suggest that NBEA is necessary either for induction of memory lability or for the physiological process of memory extinction.

Original languageEnglish
Article number13752
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

All Science Journal Classification (ASJC) codes

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    Lee, B., Bang, E., Yang, W. S., Paydar, A., Ha, G. E., Kim, S., Kim, J. H., Cho, T., Lee, S. E., Lee, S., Kang, M. G., Cheong, E., Kim, K. S., Lee, C., Yu, M. H., & Shin, H. S. (2018). The Possible Role of Neurobeachin in Extinction of Contextual Fear Memory. Scientific reports, 8(1), [13752]. https://doi.org/10.1038/s41598-018-30589-1