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  MicroRNA loss enhances learning and memory in mice

Konopka, W., Kiryk, A., Novak, M., Herwerth, M., Parkitna, J. R., Wawrzyniak, M., et al. (2010). MicroRNA loss enhances learning and memory in mice. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience, 30(44), 14835-14842. doi:10.1523/JNEUROSCI.3030-10.2010.

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Genre: Journal Article
Alternative Title : MicroRNA loss enhances learning and memory in mice

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 Creators:
Konopka, Witold, Author
Kiryk, Anna, Author
Novak, Martin, Author
Herwerth, Marina1, Author              
Parkitna, Jan Rodriguez, Author
Wawrzyniak, Marcin, Author
Kowarsch, Andreas, Author
Michaluk, Piotr, Author
Dzwonek, Joanna, Author
Arnsperger, Tabea, Author
Wilczynski, Grzegorz, Author
Merkenschlager, Matthias, Author
Theis, Fabian J., Author
Köhr, Georg1, Author              
Kaczmarek, Leszek, Author
Schütz, Günther, Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

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 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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Language(s): eng - English
 Dates: 2010-06-142010-08-242010-11-03
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 664552
DOI: 10.1523/JNEUROSCI.3030-10.2010
URI: https://www.ncbi.nlm.nih.gov/pubmed/21048142
Other: 7613
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Title: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
  Other : J. Neurosci.
Source Genre: Journal
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Publ. Info: Baltimore, MD : The Society
Pages: - Volume / Issue: 30 (44) Sequence Number: - Start / End Page: 14835 - 14842 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187_1