miR-132 Mediates the Integration of Newborn Neurons into the Adult Dentate Gyrus

Luikart, Bryan W.; Bensen, Ae Soon L.; Washburn, Eric K.; Perederiy, Julia V.; Su, Kimmy; Li, Yun; Kernie, Steven G.; Parada, Luis F.; Westbrook, Gary L.

doi:10.1371/journal.pone.0019077

Cited by 141 publications

(139 citation statements)

References 51 publications

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“…This parallels the time course of expression of WT miR-132, which increases in expression within doublecortinand NeuN-positive cells, but is absent in nestin-positive precursors (Luikart et al 2011). Collectively, these observations suggest that the miR-132/-212 locus is excised by the Cre driver in maturing granule cells in our cKO animals.…”

Section: Discussionsupporting

confidence: 74%

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

et al. 2016

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miR-132 and miR-212 are structurally related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same noncoding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/-212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/-212 double-knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/-212 double-knockout line to explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/-212 deletion increased the expression of 1138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/-212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that these two genes may function in a complex, nonredundant manner to shape the transcriptional profile of the CNS. The dysregulation of miR-132/-212 expression could contribute to signaling mechanisms that are involved in an array of cognitive disorders.

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Section: Discussionsupporting

confidence: 74%

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

et al. 2016

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“…Because of their seemingly antagonistic actions, we set out to determine whether miR-134 and miR-132 were, in fact, expressed concurrently. Earlier studies indicated that miR-132 was expressed generally throughout the brain, including large pyramidal neurons (17,18,27,29). Because the preponderance of neurons in the cortex are excitatory, we hypothesized that miR-134, at a minimum, would be expressed in this neuronal subtype.…”

Section: Discussionmentioning

confidence: 96%

MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9

Chai

Cambronne

Eichhorn

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Most brain regions comprise numerous neural cell types that are distinct in function and molecular characteristics. We examined microRNA-134 (miR-134) activity in cortical cultures using a microRNA sensor and discovered that miR-134 was induced in response to neuronal activity in somatostatin- and calretinin-expressing interneurons but not in pyramidal neurons. We identified the palmitoylation enzyme DHHC9 as a direct target of miR-134 and showed that it contributed to the regulation of H-Ras in somatostatin interneurons. H-Ras is a signaling molecule crucial for neuronal development and function. This study uncovered an activity-dependent miR-134 regulatory pathway in cortical interneurons that can potentially affect membrane localization of multiple signaling molecules.

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“…[123][124][125] Mechanistically, miR-132 is rapidly induced by BDNF in order to regulate dendritic morphogenesis by targeting a Rho GTPase protein, p250GAP (Fig. 1).…”

Section: Mir-34amentioning

confidence: 99%

Role of miRNAs and epigenetics in neural stem cell fate determination

Lopez-Ramirez

Nicoli

2013

Epigenetics

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miR-132 Mediates the Integration of Newborn Neurons into the Adult Dentate Gyrus

Cited by 141 publications

References 51 publications

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9

Role of miRNAs and epigenetics in neural stem cell fate determination

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