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Genome Biol. 2017 Nov 17;18(1):222. doi: 10.1186/s13059-017-1350-8.

Forebrain-specific, conditional silencing of Staufen2 alters synaptic plasticity, learning, and memory in rats.

Author information

1
Department of Molecular Biology, CIMH and Medical Faculty Mannheim, Heidelberg University, 68159, Mannheim, Germany.
2
Division of Neurosciences, Pablo de Olavide University, 41013, Seville, Spain.
3
Present Address: Institute Cajal (CSIC), 28002, Madrid, Spain.
4
BioMedical Center, Medical Faculty, Ludwig Maximilians University, 82152, Planegg-Martinsried, Germany.
5
Institute for Anatomy and Cell Biology, University Medicine Greifswald, 17487, Greifswald, Germany.
6
BioMedical Center, Medical Faculty, Ludwig Maximilians University, 82152, Planegg-Martinsried, Germany. inmaculada.segura@med.uni-muenchen.de.
7
BioMedical Center, Medical Faculty, Ludwig Maximilians University, 82152, Planegg-Martinsried, Germany. mkiebler@lmu.de.
8
Department of Molecular Biology, CIMH and Medical Faculty Mannheim, Heidelberg University, 68159, Mannheim, Germany. dusan.bartsch@zi-mannheim.de.

Abstract

BACKGROUND:

Dendritic messenger RNA (mRNA) localization and subsequent local translation in dendrites critically contributes to synaptic plasticity and learning and memory. Little is known, however, about the contribution of RNA-binding proteins (RBPs) to these processes in vivo.

RESULTS:

To delineate the role of the double-stranded RBP Staufen2 (Stau2), we generate a transgenic rat model, in which Stau2 expression is conditionally silenced by Cre-inducible expression of a microRNA (miRNA) targeting Stau2 mRNA in adult forebrain neurons. Known physiological mRNA targets for Stau2, such as RhoA, Complexin 1, and Rgs4 mRNAs, are found to be dysregulated in brains of Stau2-deficient rats. In vivo electrophysiological recordings reveal synaptic strengthening upon stimulation, showing a shift in the frequency-response function of hippocampal synaptic plasticity to favor long-term potentiation and impair long-term depression in Stau2-deficient rats. These observations are accompanied by deficits in hippocampal spatial working memory, spatial novelty detection, and in tasks investigating associative learning and memory.

CONCLUSIONS:

Together, these experiments reveal a critical contribution of Stau2 to various forms of synaptic plasticity including spatial working memory and cognitive management of new environmental information. These findings might contribute to the development of treatments for conditions associated with learning and memory deficits.

KEYWORDS:

BCM rule; Cognitive flexibility; Conditional inducible rat knockdown; LTD; LTP; Operant learning; RNA-binding protein; Staufen2; Working memory

PMID:
29149906
PMCID:
PMC5693596
DOI:
10.1186/s13059-017-1350-8
[Indexed for MEDLINE]
Free PMC Article

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