miR-132/212 Knockout Mice Reveal Roles for These miRNAs in Regulating Cortical Synaptic Transmission and Plasticity

Remenyi, J; van den Bosch, MWM; Palygin, O; Mistry, RB; McKenzie, C; Macdonald, A; Hutvagner, G; Arthur, JSC; Frenguelli, BG; Pankratov, Y

miR-132/212 Knockout Mice Reveal Roles for These miRNAs in Regulating Cortical Synaptic Transmission and Plasticity

Remenyi, J van den Bosch, MWM Palygin, O Mistry, RB McKenzie, C Macdonald, A Hutvagner, G

Arthur, JSC Frenguelli, BG Pankratov, Y

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Publication Type:: Journal Article
Citation:: PLoS ONE, 2013, 8 (4)
Issue Date:: 2013-04-26

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Field	Value	Language
dc.contributor.author	Remenyi, J	en_US
dc.contributor.author	van den Bosch, MWM	en_US
dc.contributor.author	Palygin, O	en_US
dc.contributor.author	Mistry, RB	en_US
dc.contributor.author	McKenzie, C	en_US
dc.contributor.author	Macdonald, A	en_US
dc.contributor.author	Hutvagner, G https://orcid.org/0000-0002-7231-9446	en_US
dc.contributor.author	Arthur, JSC	en_US
dc.contributor.author	Frenguelli, BG	en_US
dc.contributor.author	Pankratov, Y	en_US
dc.date.available	2013-03-25	en_US
dc.date.issued	2013-04-26	en_US
dc.identifier.citation	PLoS ONE, 2013, 8 (4)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/116010
dc.description.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 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. © 2013 Remenyi et al.	en_US
dc.relation.ispartof	PLoS ONE	en_US
dc.relation.isbasedon	10.1371/journal.pone.0062509	en_US
dc.subject.classification	General Science & Technology	en_US
dc.subject.mesh	Hippocampus	en_US
dc.subject.mesh	Neocortex	en_US
dc.subject.mesh	Neurons	en_US
dc.subject.mesh	Synapses	en_US
dc.subject.mesh	Fibroblasts	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Sendai virus	en_US
dc.subject.mesh	Interferon-beta	en_US
dc.subject.mesh	Receptors, AMPA	en_US
dc.subject.mesh	MicroRNAs	en_US
dc.subject.mesh	Electric Stimulation	en_US
dc.subject.mesh	Synaptic Transmission	en_US
dc.subject.mesh	Excitatory Postsynaptic Potentials	en_US
dc.subject.mesh	Neuronal Plasticity	en_US
dc.subject.mesh	Long-Term Potentiation	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Primary Cell Culture	en_US
dc.title	miR-132/212 Knockout Mice Reveal Roles for These miRNAs in Regulating Cortical Synaptic Transmission and Plasticity	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	8	en_US
utslib.for	0903 Biomedical Engineering	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	8	en_US

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 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. © 2013 Remenyi et al.

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http://hdl.handle.net/10453/116010