Top

Published in:

01-09-2009 | Original Paper

microRNA Regulation of Synaptic Plasticity

Authors: Neil R. Smalheiser, Giovanni Lugli

Published in: NeuroMolecular Medicine | Issue 3/2009

Abstract

microRNAs play an important role in regulating synaptic plasticity. For example, microRNAs target (and are targeted by) plasticity mediators such as CREB, MECP2, and FMRP. As well, specific microRNAs have been shown to be expressed within dendrites, where they regulate protein translation of targets mediating dendritic growth. Components of the RISC machinery have been implicated in long-term memory in Drosophila. Here, we review evidence from studies of adult mouse forebrain supporting a model wherein synaptic stimulation (above a threshold value) increases calcium within dendritic spines, activates calpain, and activates and releases dicer from the postsynaptic density. Dicer processes local pre-miRs into mature miRNAs that are incorporated into RISC complexes within or near the dendritic spine, and that bind available target mRNAs in the vicinity. These may repress protein translation under resting conditions, yet permit a phasic burst of translation to occur transiently following subsequent synaptic activity. Loaded RISC complexes that are not bound to local mRNAs may serve to bind and trap mRNAs that are being transported down dendrites. Thus, locally formed microRNAs may mark the location of previously activated synapses and perform a type of synaptic tagging and capture.

Abu-Elneel, K., Liu, T., Gazzaniga, F. S., Nishimura, Y., Wall, D. P., Geschwind, D. H., et al. (2008). Heterogeneous dysregulation of microRNAs across the autism spectrum. Neurogenetics, 9, 153–161. doi:10.1007/s10048-008-0133-5.PubMedCrossRef

Asaki, C., Usuda, N., Nakazawa, A., Kametani, K., & Suzuki, T. (2003). Localization of translational components at the ultramicroscopic level at postsynaptic sites of the rat brain. Brain Research, 972, 168–176. doi:10.1016/S0006-8993(03)02523-X.PubMedCrossRef

Ashraf, S. I., McLoon, A. L., Sclarsic, S. M., & Kunes, S. (2006). Synaptic protein synthesis associated with memory is regulated by the RISC pathway in Drosophila. Cell, 124, 191–205. doi:10.1016/j.cell.2005.12.017.PubMedCrossRef

Barco, A., Lopez de Armentia, M., & Alarcon, J. M. (2008). Synapse-specific stabilization of plasticity processes: The synaptic tagging and capture hypothesis revisited 10 years later. Neuroscience and Biobehavioral Reviews, 32, 831–851. doi:10.1016/j.neubiorev.2008.01.002.PubMedCrossRef

Beveridge, N. J., Tooney, P. A., Carroll, A. P., Gardiner, E., Bowden, N., Scott, R. J., et al. (2008). Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Human Molecular Genetics, 17, 1156–1168. doi:10.1093/hmg/ddn005.PubMedCrossRef

Bourne, J. N., Sorra, K. E., Hurlburt, J., & Harris, K. M. (2007). Polyribosomes are increased in spines of CA1 dendrites 2 h after the induction of LTP in mature rat hippocampal slices. Hippocampus, 2007(17), 1–4. doi:10.1002/hipo.20238.CrossRef

Dincbas-Renqvist, V., Pépin, G., Rakonjac, M., Plante, I., Ouellet, D. L., Hermansson, A., et al. (2009). Human Dicer C-terminus functions as a 5-lipoxygenase binding domain. Biochimica et Biophysica Acta, 1789, 99–108.PubMed

Duman, R. S. (2002). Pathophysiology of depression: the concept of synaptic plasticity. European Psychiatry, 17(Suppl 3), 306–310. doi:10.1016/S0924-9338(02)00654-5.PubMedCrossRef

Eis, P. S., Tam, W., Sun, L., Chadburn, A., Li, Z., Gomez, M. F., et al. (2005). Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proceedings of the National Academy of Sciences of the United States of America, 102, 3627–3632. doi:10.1073/pnas.0500613102.PubMedCrossRef

Glanzer, J., Miyashiro, K. Y., Sul, J. Y., Barrett, L., Belt, B., Haydon, P., et al. (2005). RNA splicing capability of live neuronal dendrites. Proceedings of the National Academy of Sciences of the United States of America, 102, 16859–16864. doi:10.1073/pnas.0503783102.PubMedCrossRef

Hansen, T., Olsen, L., Lindow, M., Jakobsen, K. D., Ullum, H., Jonsson, E., et al. (2007). Brain expressed microRNAs implicated in schizophrenia etiology. PLoS ONE, 2, e873. doi:10.1371/journal.pone.0000873.PubMedCrossRef

John, B., Enright, A. J., Aravin, A., Tuschl, T., Sander, C., & Marks, D. S. (2004). Human MicroRNA targets. PLoS Biology, 2, e363. doi:10.1371/journal.pbio.0020363.PubMedCrossRef

Khan, A. A., Betel, D., Sander, C., Leslie, C. S., & Marks, D. S. (2009). Nature Biotechnology, (in press).

Kim, V. N., Han, J., & Siomi, M. C. (2009). Biogenesis of small RNAs in animals. Nature Reviews. Molecular Cell Biology, 10, 126–139. doi:10.1038/nrm2632.PubMedCrossRef

Kim, S. H., Markham, J. A., Weiler, I. J., & Greenough, W. T. (2008). Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome. Proceedings of the National Academy of Sciences of the United States of America, 105, 4429–4434. doi:10.1073/pnas.0800257105.PubMedCrossRef

Kiyosawa, H., Mise, N., Iwase, S., Hayashizaki, Y., & Abe, K. (2005). Disclosing hidden transcripts: mouse natural sense–antisense transcripts tend to be poly(A) negative and nuclear localized. Genome Research, 15, 463–474. doi:10.1101/gr.3155905.PubMedCrossRef

Klein, M. E., Lioy, D. T., Ma, L., Impey, S., Mandel, G., & Goodman, R. H. (2007). Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA. Nature Neuroscience, 10, 1513–1514. doi:10.1038/nn2010.PubMedCrossRef

Kosik, K. S. (2006). The neuronal microRNA system. Nature Reviews. Neuroscience, 7, 911–920. doi:10.1038/nrn2037.PubMedCrossRef

Kye, M. J., Liu, T., Levy, S. F., Xu, N. L., Groves, B. B., Bonneau, R., et al. (2007). Somatodendritic microRNAs identified by laser capture and multiplex RT-PCR. RNA, 13, 1224–1234. doi:10.1261/rna.480407.PubMedCrossRef

Li, Y., Lin, L., & Jin, P. (2008). The microRNA pathway and fragile X mental retardation protein. Biochimica et Biophysica Acta, 1779, 702–705.PubMed

Lugli, G., Larson, J., Martone, M. E., Jones, Y., & Smalheiser, N. R. (2005). Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and are modified by neuronal activity in a calpain-dependent manner. Journal of Neurochemistry, 94, 896–905. doi:10.1111/j.1471-4159.2005.03224.x.PubMedCrossRef

Lugli, G., Torvik, V. I., Larson, J., & Smalheiser, N. R. (2008). Expression of microRNAs and their precursors in synaptic fractions of adult mouse forebrain. Journal of Neurochemistry, 106, 650–661. doi:10.1111/j.1471-4159.2008.05413.x.PubMedCrossRef

Martin, K. C., & Kosik, K. S. (2002). Synaptic tagging—Who’s it? Nature Reviews. Neuroscience, 3, 813–820. doi:10.1038/nrn942.PubMedCrossRef

Narayanan, U., Nalavadi, V., Nakamoto, M., Pallas, D. C., Ceman, S., Bassell, G. J., et al. (2007). FMRP phosphorylation reveals an immediate-early signaling pathway triggered by group I mGluR and mediated by PP2A. Journal of Neuroscience, 27, 14349–14357. doi:10.1523/JNEUROSCI.2969-07.2007.PubMedCrossRef

Nomura, T., Kimura, M., Horii, T., Morita, S., Soejima, H., Kudo, S., et al. (2008). MeCP2-dependent repression of an imprinted miR-184 released by depolarization. Human Molecular Genetics, 17, 1192–1199. doi:10.1093/hmg/ddn011.PubMedCrossRef

Omi, K., Tokunaga, K., & Hohjoh, H. (2004). Long-lasting RNAi activity in mammalian neurons. FEBS Letters, 558, 89–95. doi:10.1016/S0014-5793(04)00017-1.PubMedCrossRef

Park, S., Park, J. M., Kim, S., Kim, J. A., Shepherd, J. D., Smith-Hicks, C. L., et al. (2008). Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD. Neuron, 59, 70–83. doi:10.1016/j.neuron.2008.05.023.PubMedCrossRef

Park, C. S., & Tang, S. J. (2008). Regulation of microRNA Expression by Induction of Bidirectional Synaptic Plasticity. Journal of Molecular Neuroscience, 38, 50–66. doi:10.1007/s12031-008-9158-3.PubMedCrossRef

Perkins, D. O., Jeffries, C. D., Jarskog, L. F., Thomson, J. M., Woods, K., Newman, M. A., et al. (2007). microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biology, 8, R27. doi:10.1186/gb-2007-8-2-r27.PubMedCrossRef

Provost, P., Dishart, D., Doucet, J., Frendewey, D., Samuelsson, B., & Radmark, O. (2002). Ribonuclease activity and RNA binding of recombinant human Dicer. EMBO Journal, 21, 5864–5874. doi:10.1093/emboj/cdf578.PubMedCrossRef

Ramachandran, V., & Chen, X. (2008). Degradation of microRNAs by a family of exoribonucleases in Arabidopsis. Science, 321, 1490–1492. doi:10.1126/science.1163728.PubMedCrossRef

Schratt, G. M., Tuebing, F., Nigh, E. A., Kane, C. G., Sabatini, M. E., Kiebler, M., et al. (2006). A brain-specific microRNA regulates dendritic spine development. Nature, 439, 283–289. doi:10.1038/nature04367.PubMedCrossRef

Smalheiser, N. R. (2008a). Regulation of mammalian microRNA processing and function by cellular signaling and subcellular localization. Biochimica et Biophysica Acta, 1779, 678–681.PubMed

Smalheiser, N. R. (2008b). Synaptic enrichment of microRNAs in adult mouse forebrain is related to structural features of their precursors. Biology Direct, 3, 44. doi:10.1186/1745-6150-3-44.PubMedCrossRef

Smalheiser, N. R., Lugli, G., Lenon, A. L., & Larson, J. (manuscript submitted).

Smalheiser, N. R., Lugli, G., Rizavi, H. S., Turecki, D., Torvik, V. I., & Dwivedi, Y. (2009). (manuscript submitted).

Smalheiser, N. R., Lugli, G., Torvik, V. I., Mise, N., Ikeda, R., & Abe, K. (2008). Natural antisense transcripts are co-expressed with sense mRNAs in synaptoneurosomes of adult mouse forebrain. Neuroscience Research, 62, 236–239. doi:10.1016/j.neures.2008.08.010.PubMedCrossRef

Smalheiser, N. R., Manev, H., & Costa, E. (2001). RNAi and brain function: Was McConnell on the right track? Trends in Neurosciences, 24, 216–218. doi:10.1016/S0166-2236(00)01739-2.PubMedCrossRef

Suzuki, T., Tian, Q. B., Kuromitsu, J., Kawai, T., & Endo, S. (2007). Characterization of mRNA species that are associated with postsynaptic density fraction by gene chip microarray analysis. Neuroscience Research, 57, 61–85. doi:10.1016/j.neures.2006.09.009.PubMedCrossRef

Vasudevan, S., Tong, Y., & Steitz, J. A. (2007). Switching from repression to activation: microRNAs can up-regulate translation. Science, 318, 1931–1934. doi:10.1126/science.1149460.PubMedCrossRef

Velleca, M. A., Wallace, M. C., & Merlie, J. P. (1994). A novel synapse-associated noncoding RNA. Molecular and Cellular Biology, 14, 7095–7104.PubMed

Vo, N., Klein, M. E., Varlamova, O., Keller, D. M., Yamamoto, T., Goodman, R. H., et al. (2005). cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proceedings of the National Academy of Sciences of the United States of America, 102, 16426–16431. doi:10.1073/pnas.0508448102.PubMedCrossRef

Wayman, G. A., Davare, M., Ando, H., Fortin, D., Varlamova, O., Cheng, H. Y., et al. (2008). An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP. Proceedings of the National Academy of Sciences of the United States of America, 105, 9093–9098. doi:10.1073/pnas.0803072105.PubMedCrossRef

Weiler, I. J., Spangler, C. C., Klintsova, A. Y., Grossman, A. W., Kim, S. H., Bertaina-Anglade, V., et al. (2004). Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses. Proceedings of the National Academy of Sciences of the United States of America, 101, 17504–17509. doi:10.1073/pnas.0407533101.PubMedCrossRef

Weinmann, L., Höck, J., Ivacevic, T., Ohrt, T., Mütze, J., Schwille, P., et al. (2009). Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell, 136, 496–507. doi:10.1016/j.cell.2008.12.023.PubMedCrossRef

Wu, J., & Xie, X. (2006). Comparative sequence analysis reveals an intricate network among REST, CREB and miRNA in mediating neuronal gene expression. Genome Biology, 7, R85. doi:10.1186/gb-2006-7-9-r85.PubMedCrossRef

Xu, X. L., Li, Y., Wang, F., & Gao, F. B. (2008). The steady-state level of the nervous-system-specific microRNA-124a is regulated by dFMR1 in Drosophila. Journal of Neuroscience, 28, 11883–11889. doi:10.1523/JNEUROSCI.4114-08.2008.PubMedCrossRef

Zeng, Y., Sankala, H., Zhang, X., & Graves, P. R. (2008). Phosphorylation of Argonaute 2 at serine-387 facilitates its localization to processing bodies. Biochemical Journal, 413, 429–436. doi:10.1042/BJ20080599.PubMedCrossRef

Zhang, H., Kolb, F. A., Brondani, V., Billy, E., & Filipowicz, W. (2002). Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. EMBO Journal, 21, 5875–5885. doi:10.1093/emboj/cdf582.PubMedCrossRef

Zhou, R., Yuan, P., Wang, Y., Hunsberger, J. G., Elkahloun, A., Wei, Y., et al. (2009). Evidence for selective microRNAs and their effectors as common long-term targets for the actions of mood stabilizers. Neuropsychopharmacology, 34, 1395–1405. doi:10.1038/npp.2008.131.PubMedCrossRef

Title: microRNA Regulation of Synaptic Plasticity
Authors: Neil R. Smalheiser
Giovanni Lugli
Publication date: 01-09-2009
Publisher: Humana Press Inc
Published in: NeuroMolecular Medicine / Issue 3/2009
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-009-8065-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

microRNA Regulation of Synaptic Plasticity

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2009

MicroRNAs in Mental Health: From Biological Underpinnings to Potential Therapies

microRNAs in Gliomas: Small Regulators of a Big Problem

microRNAs in CNS Disorders

Gene Dysregulation in Huntington’s Disease: REST, MicroRNAs and Beyond

The Therapeutic Potential of microRNAs in Nervous System Damage, Degeneration, and Repair

Macro Role(s) of MicroRNAs in Fragile X Syndrome?