Transgenic miR132 Alters Neuronal Spine Density and Impairs Novel Object Recognition Memory

Hansen, Katelin F.; Sakamoto, Kensuke; Wayman, Gary A.; Impey, Soren; Obrietan, Karl

doi:10.1371/journal.pone.0015497

Cited by 199 publications

(195 citation statements)

References 31 publications

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“…miR-134 provides a compelling model for these functions because unlike miR-132, it has been localized to the synaptodendritic compartment. Of note, miR-132 has been shown to increase the size and density of dendritic spines (27,28), whereas miR-134 appears to have the opposite effect (1,9). Because of their seemingly antagonistic actions, we set out to determine whether miR-134 and miR-132 were, in fact, expressed concurrently.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Mir-132 levels in the hippocampal formation are also increased by other behavioural tasks, such as the Barnes maze or novel object recognition [62], suggesting an involvement of miR-132 in spatial memory formation. However, mice expressing miR-132 above the physiologically relevant level unexpectedly performed worse in the novel object recognition task [54,62] and the Barnes maze [62]. Excessive spine growth might be one of the side-effects of transgenic miR-132 overexpression that might limit the functional working range of neurons [62].…”

Section: (I) Mir-132mentioning

confidence: 99%

MicroRNAs and synaptic plasticity—a mutual relationship

Aksoy‐Aksel

Zampa

Schratt

2014

Phil. Trans. R. Soc. B

105

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MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain-and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.

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“…The novel object recognition test was performed as previously described (Hansen et al 2010). Briefly, mice were exposed to two identical objects for 10 min and returned to home cages.…”

Section: Novel Object Recognitionmentioning

confidence: 99%

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

et al. 2012

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Environmental enrichment (EE) has marked beneficial effects on cognitive capacity. Given the possibility that this form of neuronal plasticity could function via the actuation of the same cellular signaling pathways that underlie learning/memory formation, we examined whether the MAPK cascade effector, mitogen/stress-activated kinase 1 (MSK1), could play a role in this process. MSK1 functions as a key signaling intermediate that couples changes in neuronal activity into inducible gene expression, neuronal plasticity, and learning/memory. Here, we show that MSK1 is expressed in excitatory cell layers of the hippocampus, progenitor cells of the subgranular zone (SGZ), and adult-born immature neurons. MSK1 2/2 mice exhibit reduced spinogenesis and decreased dendritic branching complexity in hippocampal neurons, compared with WT mice. Further, in MSK1 2/2 mice, progenitor cell proliferation within the SGZ was significantly reduced and, correspondingly, the number of immature neurons within the dentate gyrus was significantly reduced. Consistent with prior work, MSK1 2/2 mice displayed deficits in both spatial and recognition memory tasks. Strikingly, cognitive enhancement resulting from a 40-d period of EE was markedly reduced in MSK1 2/2 animals. MSK1 2/2 mice exhibited reduced levels of EE-induced spinogenesis and SGZ progenitor proliferation. Taken together, these data reveal that MSK1 serves as a critical regulator of hippocampal physiology and function and that MSK1 serves as a key conduit by which enriching stimuli augment cellular plasticity and cognition.

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Transgenic miR132 Alters Neuronal Spine Density and Impairs Novel Object Recognition Memory

Cited by 199 publications

References 31 publications

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

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

MicroRNAs and synaptic plasticity—a mutual relationship

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

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