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Fear conditioning downregulates miR-138 expression in the hippocampus to facilitate the formation of fear memory.
- Source :
-
Neuroreport [Neuroreport] 2018 Nov 07; Vol. 29 (16), pp. 1418-1424. - Publication Year :
- 2018
-
Abstract
- Fear memory is important for the survival of animals and is associated with certain anxiety disorders, such as posttraumatic stress disorder. A thorough understanding of the molecular mechanisms of fear memory, especially associative fear memory, is imperative. MicroRNA-138 (miR-138) is a widely distributed microRNA in the brain and is locally enriched at synaptic sites. The role of miR-138 in the formation of fear memory is still largely unknown. In this study, a contextual fear conditioning (CFC) paradigm, bioinformatic methods, a luciferase assay, real-time PCR and western blot were used to evaluate the detailed effects of miR-138 on fear memory. We found that miR-138 transiently decreased in the dorsal hippocampus (DH) after CFC training. Upregulation or downregulation of miR-138 in the DH with miR-138 agomir or antagomir treatment significantly impaired or enhanced the formation of CFC memory, respectively. Moreover, the effects of miR-138 in the DH on the formation of CFC memory were achieved by changing the expression of the downstream target gene calpain 1 (Capn1). Taken together, both the in-vitro evidence and the in-vivo evidence presented in this study support the involvement of miR-138 in CFC memory formation, at least partly via the regulation of Capn1-mediated synaptic plasticity changes. Therapeutic use of miR-138/Capn1 is promising as an alternative option in the treatment of fear memory-related anxiety disorders.
- Subjects :
- Animals
Calpain genetics
Calpain metabolism
Conditioning, Psychological physiology
Exploratory Behavior
HEK293 Cells
Hippocampus physiology
Humans
Male
Membrane Proteins metabolism
Mice
Mice, Inbred C57BL
MicroRNAs genetics
Statistics, Nonparametric
Transfection
Down-Regulation physiology
Fear psychology
Hippocampus metabolism
Memory physiology
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1473-558X
- Volume :
- 29
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Neuroreport
- Publication Type :
- Academic Journal
- Accession number :
- 30199441
- Full Text :
- https://doi.org/10.1097/WNR.0000000000001129