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  • E-mailClive.Bramham@uib.no
  • Phone+47 55 58 60 32+47 481 25 046
  • Visitor Address
    Department of Biomedicine
    Jonas Lies vei 91
    5009 Bergen, Norway
  • Postal Address
    Postboks 7804
    5020 Bergen

The overriding goal is to explain how information is physically stored and represented in the brain, and how these processes are disrupted, altered, or destroyed in disorders of cognition including memory loss. Our research focus is the molecular control of synaptic plasticity. We aim to uncover the logic of synaptic plasticity at the level of protein synthesis, protein functional properties, and the dynamics of protein interaction networks.

Specific research areas:

  • Arc as a master regulator of long-term synaptic plasticity and cognition
  • Translational control of synaptic plasticity
  • Non-coding RNA regulation and function in synaptic plasticity
Papers by topic

 

ARC 

Hallin, EI, Eriksen, M., Baryshnikov, S., Nikolaienko, Grødem, S., Hosokawa, Y.

Hayashi, Y., *Bramham, C.R. and *Kursula, P.  (2018) Structure of monomeric full-length ARC sheds light on molecular flexibility, protein interactions, and functional modalities.

J. Neurochem. doi.org/10.1111/jnc.14556.  

 

Nikolaienko, O., Patil, S, Eriksen, M.S., and Bramham, C.R., (2018) Arc protein: a flexible hub for synaptic plasticity and cognition. Semin Cell Dev Biol, 77:33-42.

dx.doi.org/10.1016/j.semcdb.2017.09.006

 

Nair, R.R., Patil S., Tiron, A, Kanhema, T., Panja, D., Schiro, L., Parobzak, K., Wilczynski, G., and Bramham, C.R. (2017) Dynamic Arc SUMOylation and selective interaction with F-actin binding protein drebrin A in LTP consolidation in vivo.

Front Synaptic Neurosci. doi: 10.3389/fnsyn.2017.00008

 

Gozdz, A., Nikolaienko, O., Urbanska, M., Cymerman, I.A., Sitkiewicz, E., Dadlez, M., Bramham. C.R., and Jaworski, J (2017) GSK3α and GSK3β phosphorylate Arc and regulate its degradation. Front Mol Neurosci. http://doi: 10.3389/fnmol.2017.00192

 

Nikolaienko O, Eriksen MS, Patil S, Bito H, and Bramham CR (2017)  Stimulus-evoked ERK-dependent phosphorylation of activity-regulated cytoskeleton-associated protein (Arc) regulates its neuronal subcellular localization. Neuroscience 360:68–80. http://doi: 10.1016/j.neuroscience.2017.07.026.

 

Myrum, C., Soulé, J., Bittins, M., Cavagnini, K., Eriksen, M.S., Goff, K., Ziemek, S., Patil, S., Szum, A., Nair, R.R. and Bramham, C.R. (2017) Arc interacts with the integral ER protein, calnexin. Frontiers Cell Neurosci. doi.org/10.3389/fncel.2017.00294.

 

Kuipers, S., Trentani, A., Tiron, A, Mao, X., Kuhl, D., and Bramham, C.R.  (2016) BDNF-induced LTP is associated with rapid Arc-dependent enhancement in adult hippocampal neurogenesis. Scientific Reports, http://doi: 10.1038/srep21222.

 

Myrum,C., Baumann, A., Bustad, H.J., Flydal, M.I., Mariaule,V., Alvira, S., Cuéllar, J., Soulé, J., Valpuesta J.M., Márquez, J.A., *Martinez, A., and *Bramham,C.R. (2015) Arc is a flexible modular protein capable of reversible self-oligomerization. Biochem J. 468, 145-158. http://doi 10.1042/BJ20141446

 

Myrum C, Giddaluru S, Jacobsen K, Espeseth T, Nyberg L, Lundervold A J, Haavik J, Nilsson L, Reinvang I, Steen V M, Johansson S, Wibrand K, *Le Hellard S, and *Bramham C R. (2015) Common variants in the ARC gene are not associated with cognitive abilities. Brain and Behavior, doi: 10.1002/brb3.376.

 

Soule J, Alme MN, Myrum C, Schubert M, Kanhema T, Bramham CR (2012) Balancing Arc synthesis, mRNA decay, and proteasomal degradation: maximal protein expression triggered by REM sleep-like bursts of muscarinic cholinergic receptor stimulation.

J Biological Chemistry, 287(26): 22354-66.

 

Wibrand, K., Pai, B., Siripornmongcolchai, T, Bittins, M., Berentsen, B., Ofte, M.L,  Weigel, A., Skaftnesmo, K.O., and Bramham C.R.   (2012) MicroRNA regulation of the synaptic plasticity related gene Arc. PLoS ONE 7(7): e41688.

 

Bramham CR, Alme MN, Bittins M, Kuipers SD, Nair RR, Pai B, Panja D, Schubert M, Soule J, Tiron A, Wibrand K (2010) The Arc of synaptic memory. Exp Brain Res 200:125-140.

 

Kuipers SD, Tiron A, Soule J, Messaoudi E, Trentani A, Bramham CR (2009) Selective survival and maturation of adult-born dentate granule cells expressing the immediate early gene Arc/Arg3.1. PLoS ONE 4(3): e4885.

 

Bramham CR, Worley PF, Moore MJ, Guzowski JF (2008) The immediate early gene Arc/Arg.1: regulation, mechanisms, and function. J Neurosci. 27(39): 10445-10455.

 

Soule J, Penke-Verdier Z, Alme M, Kanhema T, Laroche S, Bramham CR (2008) Object-place recognition learning triggers rapid induction of plasticity-related immediate early genes and synaptic proteins  in the rat dentate gyrus.   Neural Plasticity, Article ID 269097, 12 pages.    

Messaoudi,E., Kanhema,T., Soule,J., Tiron,A., Dagyte,G., da Silva,B., and Bramham,C.R.  (2007) Sustained Arc synthesis controls LTP consolidation through regulation of local actin polymerization in the dentate gyrus in vivo.  J. Neurosci. 27: 10445-10455.  

 

Ying SW, Futter M, Rosenblum K, Webber MJ, Hunt SP, Bliss TV, Bramham CR (2002) Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: requirement for ERK activation coupled to CREB and upregulation of Arc synthesis. J Neurosci 22: 1532-1540.

 

 

BDNF

Panja, D and Bramham, C.R. (2017) BDNF function in long-term synaptic plasticity in the dentate gyrus in vivo:  methods for local drug delivery and biochemical analysis of translation. In: Neuromethods. Humana Press. doi.org/10.1007/7657_2017_7

 

Kuipers, S., Trentani, A., Tiron, A, Mao, X., Kuhl, D., and Bramham, C.R.  (2016) BDNF-induced LTP is associated with rapid Arc-dependent enhancement in adult hippocampal neurogenesis. Scientific Reports, doi: 10.1038/srep21222.

 

Panja, D., Kenney, J.W., D’Andrea, L., Zalfa, F., Vedeler, A., Wibrand, K., Fukunaga, R., Bagni, C., Proud, C.G., and Bramham, C.R. (2014). Two-stage translational control of dentate gyrus LTP consolidation is mediated by sustained BDNF-TrkB signaling to MNK. Cell Rep. 9, 1430–1445.

 

Panja, D., and Bramham, C. R. (2014). BDNF mechanisms in late LTP formation: a synthesis and breakdown. Neuropharmacology, 76: 664-676 . doi:10.1016/j.neuropharm.2013.06.024

 

Coppens, C. M., Siripornmongcolchai, T., Wibrand, K., Alme, M. N., Buwalda, B., de Boer, S. F., Koolhaas, J. M., and Bramham, C. R. (2011) Social defeat during adolescence and adulthood differentially induce BDNF-regulated immediate early genes. Front Behav. Neurosci. 5:72., Epub Nov 2.

 

Messaoudi,E., Kanhema,T., Soule,J., Tiron,A., Dagyte,G., da Silva,B., and Bramham,C.R.  (2007) Sustained Arc synthesis controls LTP consolidation through regulation of local actin polymerization in the dentate gyrus in vivo.  J. Neurosci. 27: 10445-10455.  

 

Alme MN, Wibrand K, Dagestad G, Bramham CR (2007) Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation. Neural Plast 2007: 26496. PMID: 18301726

 

Wibrand K, Messaoudi E, Havik B, Steenslid V, Løvlie R, Steen VM, and Bramham CR (2006) Identification of genes co-upregulated with Arc during BDNF-induced long-term potentiation in the adult rat dentate gyrus in vivo. Eur J Neurosci 23: 1501-1511.

 

Kanhema, T.,  Dagestad, G., Panja, D., Messaoudi, E., Haavik, B., Ying, S.W.,  Nairn, A.C., Sonenberg, N. and Bramham, C.R.  (2006) Dual regulation of translation initiation and peptide chain elongation during BDNF-induced LTP in vivo: evidence for compartment-specific translation control.  J Neurochem. 99:1328-1337.   

 

Bramham,C.R  and Messaoudi, E. (2005) BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis.  Prog. Neurobiol, 76: 99-125. 

 

Gooney, M., Messaoudi, E., Maher, F.O., *Bramham, C.R., and *Lynch, M.A. (2004) BDNF-induced LTP in dentate gyrus is impaired with age: analysis of changes in cell signalling events. Neurbiol Aging.  25: 1323-1331.

 

Ying SW, Futter M, Rosenblum K, Webber MJ, Hunt SP, Bliss TV, Bramham CR (2002) Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: requirement for ERK activation coupled to CREB and upregulation of Arc synthesis. J Neurosci 22: 1532-1540.

 

Messaoudi E, Ying SW, Kanhema T, Croll SD, Bramham CR (2002) BDNF triggers transcription-dependent, late phase LTP in vivo. J Neurosci 22: 7453-7461.

 

Messaoudi, E., Bårdsen, K.,  Srebro, B., and C.R. Bramham (1998) Acute intrahippocampal infusion of brain-derived neurotrophic factor induces lasting potentiation of synaptic transmission in the rat dentate gyrus.  J. Neurophysiol. 79: 496-499.

 

Translational control and dendritic protein synthesis

 

Bramham, C.R., Jensen, K, and Proud, CG. (2016) Tuning specific translation in cancer metastasis and synaptic memory: control at the MNK-eIF4E axis.  Trends in Biochemistry, 41: 847-858. dx.doi.org/10.1016/j.tibs.2016.07.008.

 

Panja, D., Kenney, J.W., D’Andrea, L., Zalfa, F., Vedeler, A., Wibrand, K., Fukunaga, R., Bagni, C., Proud, C.G., and Bramham, C.R. (2014). Two-stage translational control of dentate gyrus LTP consolidation is mediated by sustained BDNF-TrkB signaling to MNK. Cell Rep. 9, 1430–1445.

 

Grønli, J., Soulé, J., and Bramham, C.R. (2014). Sleep and protein synthesis-dependent synaptic plasticity: impacts of sleep loss and stress. Front. Behav. Neurosci. 7, 1–18.

 

Grønli,J., Dagestad,G., Milde,A.M., Murison,R., and Bramham,C.R. (2012). Post-transcriptional effects and interactions between chronic mild stress and acute sleep deprivation: Regulation of translation factor and cytoplasmic polyadenylation element-binding protein phosphorylation. Behav. Brain Res. 235, 251-262.

 

Panja, D., Dagyte, G., Bidinosti, M.,. Wibrand, K.,  Kristiansen, A.M., Sonenberg, N., and Bramham, C.R.  (2009) Novel translational control in Arc-dependent long-term potentiation consolidation in vivo.  J. Biological Chemistry 284: 31498-31511.  

 

Bramham, C.R.  (2008) Local protein synthesis, actin dynamics, and LTP consolidation.

Curr Opin Neurobiol. 18: 524-531.

 

Bramham C. R. and Wells D. G. (2007) Dendritic mRNA: transport, translation, and function. Nature Rev Neurosci, 8 (10): 776 – 789.

 

Dagestad,G., Messaoudi,E., and Bramham,C.R. (2006). Chronic fluoxetine induces region specific changes in translation factor eIF4E and eEF2 activity in the rat brain.  Eur J Neurosci., 23: 2814-2818.

 

Kanhema, T.,  Dagestad, G., Panja, D., Messaoudi, E., Haavik, B., Ying, S.W.,  Nairn, A.C., Sonenberg, N. and Bramham, C.R.  (2006) Dual regulation of translation initiation and peptide chain elongation during BDNF-induced LTP in vivo: evidence for compartment-specific translation control.  J Neurochem. 99:1328-1337.   

 

Håvik, B., Røkke, H., Bårdsen, K., Davanger, S. and Bramham, C.R. (2003) High-frequency bursts trigger rapid delivery of pre-existing CaMKII mRNA to synapses: a mechanism in dendritic protein synthesis during long-term potentiation in adult awake rats.  Eur. J. Neurosci., 17: 2679-2689.

 

 

Gene expression and non-coding RNAs

 

Maag, J.L.V. Panja, D, Kaczorowski, D.C. Peters, T.J., Bramham, C.R., Wibrand, K.,    and Dinger, M.E.  (2017) Widespread promoter methylation of synaptic plasticity genes in long-term potentiation in the adult brain in vivo. BMC Genomics. 18 (2017) 250. doi:10.1186/s12864-017-3621-x.

 

Maag, J.L.V., Panja,D., Sporild, I, Patil, S., Kaczorowski, D.C., *Bramham, C.R., *Dinger, M., and *Wibrand, K. (2015) Dynamic expression of long noncoding RNAs and repeat elements in synaptic plasticity. Frontiers in Neuroscience.  9:351. doi:10.3389/fnins.2015.00351

 

Pai, B., Siripornmongcolchai, T., Berentsen, B., Pakzad, A., Vieuille, C., Pallesen, S., Pajak, M., Simpson, T.I., Armstrong, J.D., Wibrand, K., and Bramham, C.R. (2014). NMDA receptor-dependent regulation of miRNA expression and association with Argonaute during LTP in vivo. Front. Cell. Neurosci. 7, 1–15.

 

Wibrand, K., Pai, B., Siripornmongcolchai, T, Bittins, M., Berentsen, B., Ofte, M.L,  Weigel, A., Skaftnesmo, K.O., and Bramham C.R.   (2012) MicroRNA regulation of the synaptic plasticity related gene Arc. PLoS ONE 7(7): e41688.

  Wibrand, K., Panja, D., Tiron, A., Ofte, M.L., Skaftnesmo, K. Sohn-Lee, C., Pena, J., Tuschl, T. and Bramham, C.R. (2010) Differential regulation of mature and precursor microRNA expression by NMDAR and metabotropic glutamate receptor expression activation during LTP in the dentate gyrus in vivo. Eur J Neurosci 31: 636-645.   Håvik, B., Røkke, H., Dagyte, G., Stavrum, A-K., *Bramham, C.R., and *Steen, V.M. (2007) Synaptic activity-induced global gene expression patterns in the dentate gyrus of adult behaving rats: induction of immunity-linked gene sets. (*Equal contribution).  Neuroscience, 148: 925-936.

 

Wibrand K, Messaoudi E, Havik B, Steenslid V, Løvlie R, Steen VM, and Bramham CR (2006) Identification of genes co-upregulated with Arc during BDNF-induced long-term potentiation in the adult rat dentate gyrus in vivo. Eur J Neurosci 23: 1501-1511.

 

Human Genetics

 

Myrum, C., Nikolaienko, O. Bramham, C.R. Haavik, J., and Zayats, T. Implication of the APP gene in intellectual abilities. (2017) J Alz Dis. 59(2):723-735. doi: 10.3233/JAD-170049.

 

Myrum C, Giddaluru S, Jacobsen K, Espeseth T, Nyberg L, Lundervold A J, Haavik J, Nilsson L, Reinvang I, Steen V M, Johansson S, Wibrand K, *Le Hellard S, and *Bramham C R. (2015) Common variants in the ARC gene are not associated with cognitive abilities. Brain and Behavior, doi: 10.1002/brb3.376.

 

Havik, B., Degenhardt, F. A., Johansson, S., Fernandes, C. P., Hinney, A., Scherag, A., Lybaek, H., Djurovic, S., Christoforou, A., Ersland, K. M., Giddaluru, S., O'Donovan, M. C., Owen, M. J., Craddock, N., Muhleisen, T. W., Mattheisen, M., Schimmelmann, B. G., Renner, T., Warnke, A., Herpertz-Dahlmann, B., Sinzig, J., Albayrak, O., Rietschel, M., Nothen, M. M., Bramham, C. R., Werge, T., Hebebrand, J., Haavik, J., Andreassen, O. A., Cichon, S., Steen, V. M., and Le Hellard S. (2012) DCLK1 Variants are associated across schizophrenia and attention deficit/hyperactivity disorder PLoS ONE 7, e35424

 

Le Hellard S, Havik B, Espeseth T, Breilid H, Lovlie R, Luciano M, Gow AJ, Harris SE, Starr JM, Wibrand K, Lundervold AJ, Porteous DJ, Bramham CR, Deary IJ, Reinvang I, Steen VM (2009) Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities. PLoS One 4:e7534.

 

Publications in CRIStin database with links:

 

In vivo electrophysiological studies of synaptic plasticity combined with genetic and local pharmacological manipulations.

Live-cell imaging in primary neuronal cultures, brain tissue slices, and intact rodents. Two-photon laser-scanning microscopy.  FRET imaging and single-particle tracking.  Single-cell electroporation.

Biochemical analysis of signal transduction mechanisms, protein-protein interactions, and functional analysis of post-translational modifications.  

  • Arc as a master regulator of long-term synaptic plasticity 
  • Translational control of synaptic plasticity
  • Non-coding RNA regulation and function in synaptic plasticity

Links to funded projects:

Molecular control of Arc protein. Research Council of Norway, Top Research Project.

Synaptic circuit protection in Alzheimer´s disease (AD) and Huntington´s disease (HD). CircProt. EU-H2020: Joint programme in Neurodegenerative disorders

 

POSTDOC AVAILABLE:  Two-photon brain imaging - FRET - Optogenetics - Synaptic plasticity

Deadline: November 4, 2018. Applications must be submitted through the JobbNorge website. Jobbnorge ID: 158877

Research groups

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