1. A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory.
- Author
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Mathew RS, Tatarakis A, Rudenko A, Johnson-Venkatesh EM, Yang YJ, Murphy EA, Todd TP, Schepers ST, Siuti N, Martorell AJ, Falls WA, Hammack SE, Walsh CA, Tsai LH, Umemori H, Bouton ME, and Moazed D
- Subjects
- Animals, Mice, Neurotransmitter Agents metabolism, Receptors, Glutamate metabolism, Fear, Feedback, Physiological, Hippocampus physiology, Memory, MicroRNAs metabolism, Neurons physiology, Synaptic Vesicles metabolism
- Abstract
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., Competing Interests: The authors declare that no competing interests exist.
- Published
- 2016
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