MiR-132 mediates the integration of newborn neurons into the adult dentate gyrus

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

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Neuronal activity enhances the elaboration of newborn neurons as they integrate into the synaptic circuitry of the adult brain. The role microRNAs play in the transduction of neuronal activity into growth and synapse formation is largely unknown. MicroRNAs can influence the expression of hundreds of genes and thus could regulate gene assemblies during processes like activity-dependent integration. Here, we developed viral-based methods for the in vivo detection and manipulation of the activity-dependent microRNA, miR-132, in the mouse hippocampus. We find, using lentiviral and retroviral reporters of miR-132 activity, that miR-132 is expressed at the right place and right time to influence the integration of newborn neurons. Retroviral knockdown of miR-132 using a specific 'sponge' containing multiple target sequences impaired the integration of newborn neurons into the excitatory synaptic circuitry of the adult brain. To assess potential miR-132 targets, we used a whole-genome microarray in PC12 cells, which have been used as a model of neuronal differentiation. miR-132 knockdown in PC12 cells resulted in the increased expression of hundreds of genes. Functional grouping indicated that genes involved in inflammatory/immune signaling were the most enriched class of genes induced by miR-132 knockdown. The correlation of miR-132 knockdown to increased proinflammatory molecular expression may indicate a mechanistic link whereby miR-132 functions as an endogenous mediator of activity-dependent integration in vivo.

Original languageEnglish (US)
Article numbere19077
JournalPLoS One
Volume6
Issue number5
DOIs
StatePublished - 2011

Fingerprint

Dentate Gyrus
MicroRNAs
microRNA
Neurons
neonates
Genes
neurons
PC12 Cells
brain
Gene Expression
gene expression
genes
Brain
Porifera
synapse
hippocampus
Synapses
Hippocampus
Genome
cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Luikart, B. W., Bensen, A. L., Washburn, E. K., Perederiy, J. V., Su, K. G., Li, Y., ... Westbrook, G. (2011). MiR-132 mediates the integration of newborn neurons into the adult dentate gyrus. PLoS One, 6(5), [e19077]. https://doi.org/10.1371/journal.pone.0019077

MiR-132 mediates the integration of newborn neurons into the adult dentate gyrus. / Luikart, Bryan W.; Bensen, AeSoon L.; Washburn, Eric K.; Perederiy, Julia V.; Su, Kimmy G.; Li, Yun; Kernie, Steven G.; Parada, Luis F.; Westbrook, Gary.

In: PLoS One, Vol. 6, No. 5, e19077, 2011.

Research output: Contribution to journalArticle

Luikart, BW, Bensen, AL, Washburn, EK, Perederiy, JV, Su, KG, Li, Y, Kernie, SG, Parada, LF & Westbrook, G 2011, 'MiR-132 mediates the integration of newborn neurons into the adult dentate gyrus', PLoS One, vol. 6, no. 5, e19077. https://doi.org/10.1371/journal.pone.0019077
Luikart BW, Bensen AL, Washburn EK, Perederiy JV, Su KG, Li Y et al. MiR-132 mediates the integration of newborn neurons into the adult dentate gyrus. PLoS One. 2011;6(5). e19077. https://doi.org/10.1371/journal.pone.0019077
Luikart, Bryan W. ; Bensen, AeSoon L. ; Washburn, Eric K. ; Perederiy, Julia V. ; Su, Kimmy G. ; Li, Yun ; Kernie, Steven G. ; Parada, Luis F. ; Westbrook, Gary. / MiR-132 mediates the integration of newborn neurons into the adult dentate gyrus. In: PLoS One. 2011 ; Vol. 6, No. 5.
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