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miRNA-132: a dynamic regulator of cognitive capacity
- Source :
- Brain structurefunction. 218(3)
- Publication Year :
- 2012
-
Abstract
- Within the central nervous system, microRNAs have emerged as important effectors of an array of developmental, physiological, and cognitive processes. Along these lines, the CREB-regulated microRNA miR-132 has been shown to influence neuronal maturation via its effects on dendritic arborization and spinogenesis. In the mature nervous system, dysregulation of miR-132 has been suggested to play a role in a number of neurocognitive disorders characterized by aberrant synaptogenesis. However, little is known about the inducible expression and function of miR-132 under normal physiological conditions in vivo. Here, we begin to explore this question within the context of learning and memory. Using in situ hybridization, we show that the presentation of a spatial memory task induced a significant ~1.5-fold increase in miR-132 expression within the CA1, CA3, and GCL excitatory cell layers of the hippocampus. To examine the role of miR-132 in hippocampal-dependent learning and memory, we employ a doxycycline-regulated miR-132 transgenic mouse strain to drive varying levels of transgenic miR-132 expression. These studies revealed that relatively low levels of transgenic miR-132 expression, paralleling the level of expression in the hippocampus following a spatial memory task, significantly enhanced cognitive capacity. In contrast, higher (supra-physiological) levels of miR-132 (>3-fold) inhibited learning. Interestingly, both the impaired cognition and elevated levels of dendritic spines resulting from supra-physiological levels of transgenic miR-132 were reversed by doxycycline suppression of transgene expression. Together, these data indicate that miR-132 functions as a key activity-dependent regulator of cognition, and that miR-132 expression must be maintained within a limited range to ensure normal learning and memory formation.
- Subjects :
- Histology
Dendritic spine
Time Factors
Transgene
Green Fluorescent Proteins
Synaptogenesis
Regulator
Hippocampus
Context (language use)
Cell Count
Mice, Transgenic
Biology
Article
Mice
Cognition
Neuroplasticity
Animals
RNA, Messenger
Maze Learning
Regulation of gene expression
Analysis of Variance
General Neuroscience
Protein-Tyrosine Kinases
Cyclic AMP-Dependent Protein Kinases
Oncogene Protein v-akt
MicroRNAs
Gene Expression Regulation
Pattern Recognition, Visual
Doxycycline
Space Perception
Anatomy
Cognition Disorders
Neuroscience
Subjects
Details
- ISSN :
- 18632661
- Volume :
- 218
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Brain structurefunction
- Accession number :
- edsair.doi.dedup.....6ed4442a8f363d8f096aead2da5358aa