miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity. PLoS One 2013;8(4):e62509
Date
05/10/2013Pubmed ID
23658634Pubmed Central ID
PMC3637221DOI
10.1371/journal.pone.0062509Scopus ID
2-s2.0-84876851786 (requires institutional sign-in at Scopus site) 136 CitationsAbstract
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 IFNβ 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.
Author List
Remenyi J, van den Bosch MW, Palygin O, Mistry RB, McKenzie C, Macdonald A, Hutvagner G, Arthur JS, Frenguelli BG, Pankratov YMESH terms used to index this publication - Major topics in bold
AnimalsElectric Stimulation
Excitatory Postsynaptic Potentials
Female
Fibroblasts
Hippocampus
Interferon-beta
Long-Term Potentiation
Male
Mice
Mice, Knockout
MicroRNAs
Neocortex
Neuronal Plasticity
Neurons
Primary Cell Culture
Receptors, AMPA
Sendai virus
Synapses
Synaptic Transmission