A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory

• Main Authors: Mathew, Rebecca S (Author), Tatarakis, Antonis (Author), Johnson-Venkatesh, Erin M (Author), Murphy, Elisabeth A (Author), Todd, Travis P (Author), Schepers, Scott T (Author), Siuti, Nertila (Author), Falls, William A (Author), Hammack, Sayamwong E (Author), Walsh, Christopher A (Author), Umemori, Hisashi (Author), Bouton, Mark E (Author), Moazed, Danesh (Author), Rudenko, Andrii (Contributor), Martorell, Anthony (Contributor), Tsai, Li-Huei (Contributor), Yang, Yawei (Contributor)
• Other Authors: Institute for Medical Engineering and Science (Contributor), Harvard University- (Contributor), Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences (Contributor), Picower Institute for Learning and Memory (Contributor)
• Format: Article
• Language: English
• Published: eLife Sciences Publications, Ltd., 2017-05-02T13:46:10Z.
• Subjects: Article
• Online Access: Get fulltext

The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway.
Brain & Behavior Research Foundation (Young Investigator Award)
JPB Foundation