An activity-regulated microRNA, miR-188, controls dendritic plasticity and synaptic transmission by downregulating neuropilin-2

• Published in: The Journal of neuroscience Vol. 32; no. 16; pp. 5678 - 5687
• Main Authors: Lee, Kihwan, Kim, Joung-Hun, Kwon, Oh-Bin, An, Kyongman, Ryu, Junghwa, Cho, Kwangwook, Suh, Yoo-Hun, Kim, Hye-Sun
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 18.04.2012
• Subjects: Analysis of Variance; Animals; Animals, Newborn; Biophysics; Cells, Cultured; Dendrites - physiology; Dendritic Spines - metabolism; Down-Regulation - genetics; Down-Regulation - physiology; Electric Stimulation - methods; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - genetics; GABA Antagonists - pharmacology; Gene Expression Profiling; Glycine - pharmacology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Hippocampus - cytology; Humans; In Vitro Techniques; Long-Term Potentiation - drug effects; Long-Term Potentiation - genetics; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Male; MicroRNAs - metabolism; Neuronal Plasticity - genetics; Neuronal Plasticity - physiology; Neurons - cytology; Neuropilin-2 - genetics; Neuropilin-2 - metabolism; Oligonucleotide Array Sequence Analysis; Patch-Clamp Techniques; Picrotoxin - pharmacology; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Strychnine - pharmacology; Synapses - genetics; Synapses - physiology; Synaptic Transmission - genetics; Synaptic Transmission - physiology; Transfection
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.6471-11.2012

MicroRNAs (miRNAs) have recently come to be viewed as critical players that modulate a number of cellular features in various biological systems including the mature CNS by exerting regulatory control over the stability and translation of mRNAs. Despite considerable evidence for the regulatory functions of miRNAs, the identities of the miRNA species that are involved in the regulation of synaptic transmission and plasticity and the mechanisms by which these miRNAs exert functional roles remain largely unknown. In the present study, the expression of microRNA-188 (miR-188) was found to be upregulated by the induction of long-term potentiation (LTP). The protein level of neuropilin-2 (Nrp-2), one of the possible molecular targets for miR-188, was decreased during LTP induction. We also confirmed that the luciferase activity of the 3'-UTR of Nrp-2 was diminished by treatment with a miR-188 oligonucleotide but not with a scrambled miRNA oligonucleotide. Nrp-2 serves as a receptor for semaphorin 3F, which is a negative regulator of spine development and synaptic structure. In addition, miR-188 specifically rescued the reduction in dendritic spine density induced by Nrp-2 expression in hippocampal neurons from rat primary culture. Furthermore, miR-188 counteracted the decrease in the miniature EPSC frequency induced by Nrp-2 expression in hippocampal neurons from rat primary culture. These findings suggest that miR-188 serves to fine-tune synaptic plasticity by regulating Nrp-2 expression.