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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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miR-26a and miR-384-5p in the hippocampus decrease after fear conditioning.Mice (8–9 weeks of age) were subjected to fear conditioning. The hippocampus was removed at 30 and 90 min after fear conditioning for miRNA analysis by qRT–PCR. The expression levels of miR-26a (a) and miR-384-5p (b) were normalized to those in untreated control mice. Data are presented as mean±s.e.m., n=4 mice for each condition. Mann–Whitney U-test is used for statistical analysis. **P<0.01, ***P<0.001.
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f9: miR-26a and miR-384-5p in the hippocampus decrease after fear conditioning.Mice (8–9 weeks of age) were subjected to fear conditioning. The hippocampus was removed at 30 and 90 min after fear conditioning for miRNA analysis by qRT–PCR. The expression levels of miR-26a (a) and miR-384-5p (b) were normalized to those in untreated control mice. Data are presented as mean±s.e.m., n=4 mice for each condition. Mann–Whitney U-test is used for statistical analysis. **P<0.01, ***P<0.001.

Mentions: LTP is a cellular mechanism that can be engaged by cognitive processing such as learning293031. To test whether miR-26a and miR-384-5p are involved in learning, we analysed the expression of miR-26a and miR-384-5p in the hippocampus after fear conditioning, a form of hippocampus-dependent associative learning that induces hippocampal LTP32333435. Mice (8–9 weeks of age) were placed in a chamber to receive tones paired with electrical foot shock. At 30 and 90 min after fear conditioning, mice were euthanized and the hippocampus was removed for miRNA analysis. miR-26a was reduced at 90 min, while miR-384-5p was reduced at both 30 and 90 min after fear conditioning (Fig. 9). Hence, fear conditioning induces decreases in miR-26a and miR-384-5p, presumably facilitating LTP and fear memory formation.


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)

miR-26a and miR-384-5p in the hippocampus decrease after fear conditioning.Mice (8–9 weeks of age) were subjected to fear conditioning. The hippocampus was removed at 30 and 90 min after fear conditioning for miRNA analysis by qRT–PCR. The expression levels of miR-26a (a) and miR-384-5p (b) were normalized to those in untreated control mice. Data are presented as mean±s.e.m., n=4 mice for each condition. Mann–Whitney U-test is used for statistical analysis. **P<0.01, ***P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f9: miR-26a and miR-384-5p in the hippocampus decrease after fear conditioning.Mice (8–9 weeks of age) were subjected to fear conditioning. The hippocampus was removed at 30 and 90 min after fear conditioning for miRNA analysis by qRT–PCR. The expression levels of miR-26a (a) and miR-384-5p (b) were normalized to those in untreated control mice. Data are presented as mean±s.e.m., n=4 mice for each condition. Mann–Whitney U-test is used for statistical analysis. **P<0.01, ***P<0.001.
Mentions: LTP is a cellular mechanism that can be engaged by cognitive processing such as learning293031. To test whether miR-26a and miR-384-5p are involved in learning, we analysed the expression of miR-26a and miR-384-5p in the hippocampus after fear conditioning, a form of hippocampus-dependent associative learning that induces hippocampal LTP32333435. Mice (8–9 weeks of age) were placed in a chamber to receive tones paired with electrical foot shock. At 30 and 90 min after fear conditioning, mice were euthanized and the hippocampus was removed for miRNA analysis. miR-26a was reduced at 90 min, while miR-384-5p was reduced at both 30 and 90 min after fear conditioning (Fig. 9). Hence, fear conditioning induces decreases in miR-26a and miR-384-5p, presumably facilitating LTP and fear memory formation.

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