MicroRNA Loss Enhances Learning and Memory in Mice
Abstract
Dicer-dependent noncoding RNAs, including microRNAs (miRNAs), play an important role in a modulation of translation of mRNA transcripts necessary for differentiation in many cell types. In vivo experiments using cell type-specific Dicer1 gene inactivation in neurons showed its essential role for neuronal development and survival. However, little is known about the consequences of a loss of miRNAs in adult, fully differentiated neurons. To address this question, we used an inducible variant of the Cre recombinase (tamoxifen-inducible CreERT2) under control of Camk2a gene regulatory elements. After induction of Dicer1 gene deletion in adult mouse forebrain, we observed a progressive loss of a whole set of brain-specific miRNAs. Animals were tested in a battery of both aversively and appetitively motivated cognitive tasks, such as Morris water maze, IntelliCage system, or trace fear conditioning. Compatible with rather long half-life of miRNAs in hippocampal neurons, we observed an enhancement of memory strength of mutant mice 12 weeks after the Dicer1 gene mutation, before the onset of neurodegenerative process. In acute brain slices, immediately after high-frequency stimulation of the Schaffer collaterals, the efficacy at CA3-to-CA1 synapses was higher in mutant than in control mice, whereas long-term potentiation was comparable between genotypes. This phenotype was reflected at the subcellular and molecular level by the elongated filopodia-like shaped dendritic spines and an increased translation of synaptic plasticity-related proteins, such as BDNF and MMP-9 in mutant animals. The presented work shows miRNAs as key players in the learning and memory process of mammals.
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General loss of miRNA function through Dicer1 ablation produces a wide range of changes in hippocampal dendrites, including increased dendritic spine length, reduced dendritic arborization, and a bias toward arborization more distal to the soma.
“General loss of miRNA function through Dicer1 ablation produces a wide range of changes in hippocampal dendrites, including but not limited to increased dendritic spine length, reduced dendritic arborization, and a bias toward arborization more distal to the soma [38, 39].”
From MiR-338-3p regulates neuronal maturation and suppresses glioblastoma proliferation. (2017) · cites this paper as [38]
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- Authors
- Konopka, W., Kiryk, A., Novak, M., Herwerth, M., Parkitna, J. R., Wawrzyniak, M., Kowarsch, A., Michaluk, P., Dzwonek, J., Arnsperger, T., Wilczynski, G., Merkenschlager, M., Theis, F. J., Köhr, G., Kaczmarek, L., & Schütz, G.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-11-03
- Volume
- 30
- Issue
- 44
- Pages
- 14835-14842
- ISSN
- 0270-6474
- 1529-2401
- Cited by
- 268
- References
- 2
- Language
- en
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