MiR‐29 coordinates age‐dependent plasticity brakes in the adult visual cortex

Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular “brakes” limiting excessive rewiring beyond a critical period. The mechanisms coordinating the expression of these factors during the transition from development to adulthood remain unknown. We found that miR‐29a expression in the visual cortex dramatically increases with age, but it is not experience‐dependent. Precocious high levels of miR‐29a blocked ocular dominance plasticity and caused an early appearance of perineuronal nets. Conversely, inhibition of miR‐29a in adult mice using LNA antagomirs activated ocular dominance plasticity, reduced perineuronal nets, and restored their juvenile chemical composition. Activated adult plasticity had the typical functional and proteomic signature of critical period plasticity. Transcriptomic and proteomic studies indicated that miR‐29a manipulation regulates the expression of plasticity brakes in specific cortical circuits. These data indicate that miR‐29a is a regulator of the plasticity brakes promoting age‐dependent stabilization of visual cortical connections.

[1]  Hagen U. Tilgner,et al.  SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse , 2019, Neuron.

[2]  L. Saksida,et al.  Perineuronal Nets: Plasticity, Protection, and Therapeutic Potential , 2019, Trends in Neurosciences.

[3]  J. Fawcett,et al.  The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function , 2019, Nature Reviews Neuroscience.

[4]  A. Prochiantz,et al.  Non-cell Autonomous OTX2 Homeoprotein Regulates Visual Cortex Plasticity Through Gadd45b/g. , 2019, Cerebral cortex.

[5]  J. Fawcett,et al.  Inhibition of Semaphorin3A Promotes Ocular Dominance Plasticity in the Adult Rat Visual Cortex , 2019, Molecular Neurobiology.

[6]  C. I. Smith,et al.  Therapeutic Oligonucleotides: State of the Art. , 2019, Annual review of pharmacology and toxicology.

[7]  Gian Michele Ratto,et al.  Perineuronal nets control visual input via thalamic recruitment of cortical PV interneurons , 2018, eLife.

[8]  D. Binder,et al.  Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice , 2018, Cerebral cortex.

[9]  Torkel Hafting,et al.  Aggrecan Directs Extracellular Matrix-Mediated Neuronal Plasticity , 2018, The Journal of Neuroscience.

[10]  D. Binder,et al.  The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders , 2018, Front. Mol. Neurosci..

[11]  Christopher Y. Park,et al.  AGO CLIP Reveals an Activated Network for Acute Regulation of Brain Glutamate Homeostasis in Ischemic Stroke. , 2019, Cell reports.

[12]  E. Quinlan,et al.  Critical periods in amblyopia , 2018, Visual Neuroscience.

[13]  S. Kim,et al.  Synapse development organized by neuronal activity-regulated immediate-early genes , 2018, Experimental & Molecular Medicine.

[14]  D. Bartel.  Metazoan MicroRNAs , 2018, Cell.

[15]  Henning Hermjakob,et al.  The Reactome pathway knowledgebase , 2013, Nucleic Acids Res..

[16]  J. Fawcett,et al.  Inhibition of Semaphorin-3A promotes ocular dominance plasticity in the adult rat visual cortex , 2018 .

[17]  P. M. Craig,et al.  Rainbow trout exposed to benzo[a]pyrene yields conserved microRNA binding sites in DNA methyltransferases across 500 million years of evolution , 2017, Scientific Reports.

[18]  G. Rossi,et al.  Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health , 2017, Scientific Reports.

[19]  Harrison W. Gabel,et al.  Early-Life Gene Expression in Neurons Modulates Lasting Epigenetic States , 2017, Cell.

[20]  J. Fawcett,et al.  Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration , 2017, Neurobiology of Aging.

[21]  K. Fouad,et al.  Enhancing Spinal Plasticity Amplifies the Benefits of Rehabilitative Training and Improves Recovery from Stroke , 2017, The Journal of Neuroscience.

[22]  E. Quinlan,et al.  Light reintroduction after dark exposure reactivates plasticity in adults via perisynaptic activation of MMP-9 , 2017, eLife.

[23]  G. Schratt,et al.  MicroRNAs in neural development: from master regulators to fine-tuners , 2017, Development.

[24]  J. Fawcett,et al.  Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory , 2017, Aging.

[25]  P. Baldi,et al.  Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception , 2017, Nature Communications.

[26]  M. Bear,et al.  Arc restores juvenile plasticity in adult mouse visual cortex , 2017, Proceedings of the National Academy of Sciences.

[27]  anastasia. khvorova,et al.  The chemical evolution of oligonucleotide therapies of clinical utility , 2017, Nature Biotechnology.

[28]  F. Slack,et al.  MicroRNA therapeutics: towards a new era for the management of cancer and other diseases , 2017, Nature Reviews Drug Discovery.

[29]  Torkel Hafting,et al.  Removal of Perineuronal Nets Unlocks Juvenile Plasticity Through Network Mechanisms of Decreased Inhibition and Increased Gamma Activity , 2017, The Journal of Neuroscience.

[30]  Gene W. Yeo,et al.  MicroRNA-101 Regulates Multiple Developmental Programs to Constrain Excitation in Adult Neural Networks , 2016, Neuron.

[31]  Marta Miquel,et al.  Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity , 2016, The Journal of Neuroscience.

[32]  A. Cellerino,et al.  MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging , 2016, BMC Biology.

[33]  Mario Costa,et al.  Experience Affects Critical Period Plasticity in the Visual Cortex through an Epigenetic Regulation of Histone Post-Translational Modifications , 2016, The Journal of Neuroscience.

[34]  Christof Koch,et al.  Adult Mouse Cortical Cell Taxonomy by Single Cell Transcriptomics , 2016, Nature Neuroscience.

[35]  F. Rossi,et al.  H3 and H4 Lysine Acetylation Correlates with Developmental and Experimentally Induced Adult Experience-Dependent Plasticity in the Mouse Visual Cortex , 2016, Journal of experimental neuroscience.

[36]  S. Berretta,et al.  In Sickness and in Health: Perineuronal Nets and Synaptic Plasticity in Psychiatric Disorders , 2015, Neural plasticity.

[37]  A. Majewska,et al.  Proteolytic regulation of synaptic plasticity in the mouse primary visual cortex: analysis of matrix metalloproteinase 9 deficient mice , 2015, Front. Cell. Neurosci..

[38]  Murray J. Cairns,et al.  MicroRNA and Posttranscriptional Dysregulation in Psychiatry , 2015, Biological Psychiatry.

[39]  Jiangteng Lu,et al.  MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex , 2015, Proceedings of the National Academy of Sciences.

[40]  S. Bhattacharyya,et al.  Decline in arylsulfatase B and Increase in chondroitin 4‐sulfotransferase combine to increase chondroitin 4‐sulfate in traumatic brain injury , 2015, Journal of neurochemistry.

[41]  M. D'Esposito,et al.  Experience-dependent DNA methylation regulates plasticity in the developing visual cortex , 2015, Nature Neuroscience.

[42]  Woong Sun,et al.  Early growth response 1 (Egr‐1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus , 2015, Journal of neurochemistry.

[43]  Marco Rossi,et al.  miR-29s: a family of epi-miRNAs with therapeutic implications in hematologic malignancies , 2015, Oncotarget.

[44]  T. Hensch,et al.  Clock Genes Control Cortical Critical Period Timing , 2015, Neuron.

[45]  Matthew E. Ritchie,et al.  limma powers differential expression analyses for RNA-sequencing and microarray studies , 2015, Nucleic acids research.

[46]  S. Berretta,et al.  Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala , 2015, Translational Psychiatry.

[47]  Tommaso Pizzorusso,et al.  Perilesional treatment with chondroitinase ABC and motor training promote functional recovery after stroke in rats. , 2015, Cerebral cortex.

[48]  J. Kaminker,et al.  Activity-Induced Nr4a1 Regulates Spine Density and Distribution Pattern of Excitatory Synapses in Pyramidal Neurons , 2014, Neuron.

[49]  J. Prehn,et al.  Increased Expression of MicroRNA-29a in ALS Mice: Functional Analysis of Its Inhibition , 2014, Journal of Molecular Neuroscience.

[50]  S. Bhattacharyya,et al.  Arylsulfatase B modulates neurite outgrowth via astrocyte chondroitin‐4‐sulfate: Dysregulation by ethanol , 2014, Glia.

[51]  A. Lovett-racke,et al.  Increased micro-RNA 29b in the aged brain correlates with the reduction of insulin-like growth factor-1 and fractalkine ligand , 2013, Neurobiology of Aging.

[52]  R. Giffard,et al.  Astrocyte‐enriched miR‐29a targets PUMA and reduces neuronal vulnerability to forebrain ischemia , 2013, Glia.

[53]  Choogon Lee,et al.  miRNAs Are Required for Generating a Time Delay Critical for the Circadian Oscillator , 2013, Current Biology.

[54]  A. Kirkwood,et al.  Obligatory Role for the Immediate Early Gene NARP in Critical Period Plasticity , 2013, Neuron.

[55]  T. Ochiya,et al.  miR-29 Represses the Activities of DNA Methyltransferases and DNA Demethylases , 2013, International journal of molecular sciences.

[56]  Takao K Hensch,et al.  Choroid-plexus-derived Otx2 homeoprotein constrains adult cortical plasticity. , 2013, Cell reports.

[57]  S. Gnyawali,et al.  Loss of miR-29b following Acute Ischemic Stroke Contributes to Neural Cell Death and Infarct Size , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[58]  T. Dierks,et al.  Arylsulfatase B Improves Locomotor Function after Mouse Spinal Cord Injury , 2013, PloS one.

[59]  Israel Steinfeld,et al.  miRNA target enrichment analysis reveals directly active miRNAs in health and disease , 2012, Nucleic acids research.

[60]  Takao K Hensch,et al.  Balancing plasticity/stability across brain development. , 2013, Progress in brain research.

[61]  T. Fukushima,et al.  Reduction of Type IV Collagen by Upregulated miR-29 in Normal Elderly Mouse and klotho-Deficient, Senescence-Model Mouse , 2012, PloS one.

[62]  M. Stryker,et al.  Development and Plasticity of the Primary Visual Cortex , 2012, Neuron.

[63]  F. Slack,et al.  Novel MicroRNAs Differentially Expressed during Aging in the Mouse Brain , 2012, PloS one.

[64]  A. Prochiantz,et al.  Otx2 Binding to Perineuronal Nets Persistently Regulates Plasticity in the Mature Visual Cortex , 2012, The Journal of Neuroscience.

[65]  Mark Hübener,et al.  Critical-period plasticity in the visual cortex. , 2012, Annual review of neuroscience.

[66]  K. Jin,et al.  Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats , 2012, Proceedings of the National Academy of Sciences.

[67]  Pierre Baldi,et al.  Cyber-T web server: differential analysis of high-throughput data , 2012, Nucleic Acids Res..

[68]  M. Platzer,et al.  Age-dependent regulation of tumor-related microRNAs in the brain of the annual fish Nothobranchius furzeri , 2012, Mechanisms of Ageing and Development.

[69]  P. Yip,et al.  Delayed treatment with chondroitinase ABC promotes sensorimotor recovery and plasticity after stroke in aged rats. , 2012, Brain : a journal of neurology.

[70]  L. Maffei,et al.  Inhibition of matrix metalloproteinases prevents the potentiation of nondeprived-eye responses after monocular deprivation in juvenile rats. , 2012, Cerebral cortex.

[71]  Yumiko Yoshimura,et al.  Persistent cortical plasticity by upregulation of chondroitin 6-sulfation , 2012, Nature Neuroscience.

[72]  Michael Q. Zhang,et al.  Cell-Type-Based Analysis of MicroRNA Profiles in the Mouse Brain , 2012, Neuron.

[73]  Michele Zoli,et al.  Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology , 2011, The Journal of cell biology.

[74]  Alessandro Coatti,et al.  Experience-dependent expression of miR132 regulates ocular dominance plasticity , 2011, Nature Neuroscience.

[75]  Ignacio Varela,et al.  Aging and chronic DNA damage response activate a regulatory pathway involving miR‐29 and p53 , 2011, The EMBO journal.

[76]  M. Mann,et al.  Andromeda: a peptide search engine integrated into the MaxQuant environment. , 2011, Journal of proteome research.

[77]  S. Hammond,et al.  miR-29b is activated during neuronal maturation and targets BH3-only genes to restrict apoptosis. , 2011, Genes & development.

[78]  M. Lachmann,et al.  MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. , 2010, Genome research.

[79]  J. Fawcett,et al.  Animals lacking link protein have attenuated perineuronal nets and persistent plasticity. , 2010, Brain : a journal of neurology.

[80]  T. Pizzorusso,et al.  Epigenetic treatments of adult rats promote recovery from visual acuity deficits induced by long‐term monocular deprivation , 2010, The European journal of neuroscience.

[81]  P. Worley,et al.  A Specific Requirement of Arc/Arg3.1 for Visual Experience-Induced Homeostatic Synaptic Plasticity in Mouse Primary Visual Cortex , 2010, The Journal of Neuroscience.

[82]  M. Sur,et al.  Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation , 2010, Nature Neuroscience.

[83]  T. Woo,et al.  Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia. , 2010, Archives of general psychiatry.

[84]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[85]  Israel Steinfeld,et al.  BMC Bioinformatics BioMed Central , 2008 .

[86]  M. Mann,et al.  MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification , 2008, Nature Biotechnology.

[87]  M. Stryker,et al.  Distinctive Features of Adult Ocular Dominance Plasticity , 2008, The Journal of Neuroscience.

[88]  A. Delacourte,et al.  Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/β-secretase expression , 2008, Proceedings of the National Academy of Sciences.

[89]  Elena Cattaneo,et al.  A microRNA-based gene dysregulation pathway in Huntington's disease , 2008, Neurobiology of Disease.

[90]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[91]  Gail Mandel,et al.  Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA , 2007, Nature Neuroscience.

[92]  C. Morrison,et al.  MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B , 2007, Proceedings of the National Academy of Sciences.

[93]  L. Maffei,et al.  Developmental Downregulation of Histone Posttranslational Modifications Regulates Visual Cortical Plasticity , 2007, Neuron.

[94]  Nicoletta Berardi,et al.  Structural and functional recovery from early monocular deprivation in adult rats. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[95]  Nobuko Mataga,et al.  Experience-Dependent Pruning of Dendritic Spines in Visual Cortex by Tissue Plasminogen Activator , 2004, Neuron.

[96]  Mriganka Sur,et al.  Dendritic Spine Dynamics Are Regulated by Monocular Deprivation and Extracellular Matrix Degradation , 2004, Neuron.

[97]  Mark F. Bear,et al.  How Monocular Deprivation Shifts Ocular Dominance in Visual Cortex of Young Mice , 2004, Neuron.

[98]  Ewelina Knapska,et al.  A gene for neuronal plasticity in the mammalian brain: Zif268/Egr-1/NGFI-A/Krox-24/TIS8/ZENK? , 2004, Progress in Neurobiology.

[99]  L. Maffei,et al.  Reactivation of Ocular Dominance Plasticity in the Adult Visual Cortex , 2002, Science.

[100]  Pierre Baldi,et al.  A Bayesian framework for the analysis of microarray expression data: regularized t -test and statistical inferences of gene changes , 2001, Bioinform..

[101]  D. Corey,et al.  Locked nucleic acid (LNA): fine-tuning the recognition of DNA and RNA. , 2001, Chemistry & biology.

[102]  L. Maffei,et al.  BDNF Regulates the Maturation of Inhibition and the Critical Period of Plasticity in Mouse Visual Cortex , 1999, Cell.

[103]  A. Ogston,et al.  Fractionation of a hyaluronic acid preparation in a density gradient. The isolation and identification of a chondroitin sulphate. , 1967, The Biochemical journal.