TY - JOUR
T1 - GSK-3β activation is required for ZIP-induced disruption of learned fear
AU - Song, Sukwoon
AU - Kim, Jihye
AU - Park, Kyungjoon
AU - Lee, Junghwa
AU - Park, Sewon
AU - Lee, Sukwon
AU - Kim, Jeongyeon
AU - Hong, Ingie
AU - Song, Beomjong
AU - Choi, Sukwoo
N1 - Funding Information:
This work was supported by the NRF of Korea grant funded by the Korea government the Ministry of Education, Science and Technology (NRF-2016R1A2C3009854) and by Samsung Science and Technology Foundation under Project Number SSTF-BA1802-12. S.S. was supported by Brain Korea 21 Research Fellowship from the Korean Ministry of Education. S.L. and J.K. were supported by KBRI basic research program through Korea Brain Research Institute funded by the Ministry of Science and ICT (20-BR-02-02, 20-BR-02-05).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The myristoylated zeta inhibitory peptide (ZIP), which was originally developed as a protein kinase C/Mζ (PKCζ/PKMζ) inhibitor, is known to produce the loss of different forms of memories. However, ZIP induces memory loss even in the absence of PKMζ, and its mechanism of action, therefore, remains elusive. Here, through a kinome-wide screen, we found that glycogen synthase kinase 3 beta (GSK-3β) was robustly activated by ZIP in vitro. ZIP induced depotentiation (a cellular substrate of memory erasure) of conditioning-induced potentiation at LA synapses, and the ZIP-induced depotentiation was prevented by a GSK-3β inhibitor, 6-bromoindirubin-3-acetoxime (BIO-acetoxime). Consistently, GSK-3β inhibition by BIO-acetoxime infusion or GSK-3β knockdown by GSK-3β shRNA in the LA attenuated ZIP-induced disruption of learned fear. Furthermore, conditioned fear was decreased by expression of a non-inhibitable form of GSK-3β in the LA. Our findings suggest that GSK-3β activation is a critical step for ZIP-induced disruption of memory.
AB - The myristoylated zeta inhibitory peptide (ZIP), which was originally developed as a protein kinase C/Mζ (PKCζ/PKMζ) inhibitor, is known to produce the loss of different forms of memories. However, ZIP induces memory loss even in the absence of PKMζ, and its mechanism of action, therefore, remains elusive. Here, through a kinome-wide screen, we found that glycogen synthase kinase 3 beta (GSK-3β) was robustly activated by ZIP in vitro. ZIP induced depotentiation (a cellular substrate of memory erasure) of conditioning-induced potentiation at LA synapses, and the ZIP-induced depotentiation was prevented by a GSK-3β inhibitor, 6-bromoindirubin-3-acetoxime (BIO-acetoxime). Consistently, GSK-3β inhibition by BIO-acetoxime infusion or GSK-3β knockdown by GSK-3β shRNA in the LA attenuated ZIP-induced disruption of learned fear. Furthermore, conditioned fear was decreased by expression of a non-inhibitable form of GSK-3β in the LA. Our findings suggest that GSK-3β activation is a critical step for ZIP-induced disruption of memory.
UR - http://www.scopus.com/inward/record.url?scp=85093961087&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85093961087&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-75130-5
DO - 10.1038/s41598-020-75130-5
M3 - Article
C2 - 33106552
AN - SCOPUS:85093961087
SN - 2045-2322
VL - 10
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 18227
ER -