miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

Judit Remenyi, Mirjam W. M. van den Bosch, Oleg Palygin, Rajen B. Mistry, Colin McKenzie, Andrew Macdonald, Gyorgy Hutvagner, J. Simon C. Arthur, Bruno G. Frenguelli, Yuriy Pankratov

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    96 Citations (Scopus)

    Abstract

    miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNß induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity.

    Original languageEnglish
    Article numbere62509
    Number of pages14
    JournalPLoS ONE
    Volume8
    Issue number4
    DOIs
    Publication statusPublished - 26 Apr 2013

    Keywords

    • ACTIVATION
    • INDUCED MICRORNA
    • COCAINE INTAKE
    • PHOSPHORYLATION
    • HIPPOCAMPUS
    • EXPRESSION
    • MOUSE
    • CREB
    • IN-VIVO
    • MSK1

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