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miR-26a and miR-384-5p are required for LTP maintenance and spine enlargement.

Gu QH, Yu D, Hu Z, Liu X, Yang Y, Luo Y, Zhu J, Li Z - Nat Commun (2015)

Bottom Line: Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength.Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities.This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate 'LTP miRNAs'.

View Article: PubMed Central - PubMed

Affiliation: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.

ABSTRACT
Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. It is associated with the formation and enlargement of dendritic spines-tiny protrusions accommodating excitatory synapses. Both LTP and spine remodelling are crucial for brain development, cognition and the pathophysiology of neurological disorders. The role of microRNAs (miRNAs) in the maintenance of LTP, however, is not well understood. Using next-generation sequencing to profile miRNA transcriptomes, we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3. Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities. This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate 'LTP miRNAs'.

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Related in: MedlinePlus

The downregulation of miR-26a and miR-384-5p is required for spine plasticity associated with LTP.(a) Experimental design. (b) Representative images. (c,d) Quantification of b. n=10–18 neurons for each condition. Data are presented as mean±s.e.m. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis. *P<0.05, *** and ##P<0.01, ###P<0.001. Scale bar, 20 μm for low-magnification images and 5 μm for high-magnification images.
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f5: The downregulation of miR-26a and miR-384-5p is required for spine plasticity associated with LTP.(a) Experimental design. (b) Representative images. (c,d) Quantification of b. n=10–18 neurons for each condition. Data are presented as mean±s.e.m. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis. *P<0.05, *** and ##P<0.01, ###P<0.001. Scale bar, 20 μm for low-magnification images and 5 μm for high-magnification images.

Mentions: At 2∼3 days after transfection, neurons were treated with TEA (25 mM, 15 min) and imaged before and after treatment. TEA treatment caused a rapid and sustained expansion of dendritic spines (increased by 37.4±3.6% (P=2.14 × 10−5) at 10 min and 51.4±4.5% (P=5.8 × 10−8) at 90 min after treatment; Fig. 8). Spine number was also increased by TEA treatment (up by 14.0±3.2% (P=0.12) at 10 min and 24.1±3.0% (P=0.03) at 90 min after treatment; Fig. 5). Transfection of the miR-215 construct did not affect TEA-induced changes in spines (Fig. 5).


miR-26a and miR-384-5p are required for LTP maintenance and spine enlargement.

Gu QH, Yu D, Hu Z, Liu X, Yang Y, Luo Y, Zhu J, Li Z - Nat Commun (2015)

The downregulation of miR-26a and miR-384-5p is required for spine plasticity associated with LTP.(a) Experimental design. (b) Representative images. (c,d) Quantification of b. n=10–18 neurons for each condition. Data are presented as mean±s.e.m. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis. *P<0.05, *** and ##P<0.01, ###P<0.001. Scale bar, 20 μm for low-magnification images and 5 μm for high-magnification images.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403380&req=5

f5: The downregulation of miR-26a and miR-384-5p is required for spine plasticity associated with LTP.(a) Experimental design. (b) Representative images. (c,d) Quantification of b. n=10–18 neurons for each condition. Data are presented as mean±s.e.m. Kruskal–Wallis and Mann–Whitney U-tests are used for statistical analysis. *P<0.05, *** and ##P<0.01, ###P<0.001. Scale bar, 20 μm for low-magnification images and 5 μm for high-magnification images.
Mentions: At 2∼3 days after transfection, neurons were treated with TEA (25 mM, 15 min) and imaged before and after treatment. TEA treatment caused a rapid and sustained expansion of dendritic spines (increased by 37.4±3.6% (P=2.14 × 10−5) at 10 min and 51.4±4.5% (P=5.8 × 10−8) at 90 min after treatment; Fig. 8). Spine number was also increased by TEA treatment (up by 14.0±3.2% (P=0.12) at 10 min and 24.1±3.0% (P=0.03) at 90 min after treatment; Fig. 5). Transfection of the miR-215 construct did not affect TEA-induced changes in spines (Fig. 5).

Bottom Line: Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength.Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities.This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate 'LTP miRNAs'.

View Article: PubMed Central - PubMed

Affiliation: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.

ABSTRACT
Long-term potentiation (LTP) is a form of synaptic plasticity that results in enhanced synaptic strength. It is associated with the formation and enlargement of dendritic spines-tiny protrusions accommodating excitatory synapses. Both LTP and spine remodelling are crucial for brain development, cognition and the pathophysiology of neurological disorders. The role of microRNAs (miRNAs) in the maintenance of LTP, however, is not well understood. Using next-generation sequencing to profile miRNA transcriptomes, we demonstrate that miR-26a and miR-384-5p specifically affect the maintenance, but not induction, of LTP and different stages of spine enlargement by regulating the expression of RSK3. Using bioinformatics, we also examine the global effects of miRNA transcriptome changes during LTP on gene expression and cellular activities. This study reveals a novel miRNA-mediated mechanism for gene-specific regulation of translation in LTP, identifies two miRNAs required for long-lasting synaptic and spine plasticity and presents a catalogue of candidate 'LTP miRNAs'.

Show MeSH
Related in: MedlinePlus