Clive R Bramham

Position

Professor, Head of Synaptic Plasticity Research Group

Affiliation

Research groups

Research

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
Publications
Papers by topic

Arc protein structure, function, and regulation

Avallone. M., Pardo, J., Mergiya, T.F., Rajova, J. Räsänen, A., Davidsson, M., Åkerblom, M., Quintino, L., Kumar, D., Bramham, C.R., & Björklund, T. (2023) Visualizing Arc protein dynamics and localization in the mammalian brain using adeno-associated virus-mediated in situ gene labeling. Front. Mol. Neurosci. Vol 16, doi:10.3389/fnmol.2023.1140785.

Mergiya, T.F., Gundersen, J.E.T., Kanhema, T., Brighter, G., Ishizuka, Y., & Bramham, C.R. (2023) Detection of Arc/Arg3.1 oligomers in rat brain: constitutive and synaptic activity-evoked dimer expression in vivo. Front. Mol. Neurosci. Vol 16, doi: 10.3389/fnmol.2023.1142361

Eriksen M.S. and Bramham C.R. (2022) Molecular physiology of Arc/Arg3.1: The oligomeric state hypothesis of synaptic plasticity. Acta Physiologica, e13886. doi.org/10.1111/apha.13886

Ishizuka, Y., Mergiya, T.F. Baldinotti, R., Xu, J., Hallin, E.I., Markússon, S., Kursula, P., and Bramham, C.R. (2022). Development and Validation of Arc Nanobodies: New Tools for Probing Arc Dynamics and Function. Neurochem Res 47, 2656–2666 doi.org/10.1007/s11064-022-03573-5.

Markússon, S, Hallin, E.I., Bustad, H.J., Raasakka, A., Xu, J., Muruganandam, G., Loris, R., Martinez, A., Bramham, C.R. and Kursula, P. (2022). High-affinity anti-Arc nanobodies provide tools for structural and functional studies. PLoS ONE 17(6): e0269281. doi.org/10.1371/journal.pone.0269281

Hallin, E.I., Markússon, S., Böttger, L., Torda, A.E., Bramham, C.R., and Kursula, K. (2021) Crystal and solution structures reveal oligomerization of individual capsid homology domains of Drosophila Arc. PLoS One 16, e0251459. doi.org/10.1371/journal.pone.0251459

Hallin, E.I., Bramham, C.R., and Kursula, K. Structural properties and peptide ligand binding of the capsid homology domains of human Arc (2021) Biochem Biophys Res Commun 26, doi.org/10.1101/2020.12.17.423319 

Eriksen MS, Nikolaienko O, Hallin EI, Grødem S, Bustad HJ, Flydal MI, Merski I, Hosokawa T, Lascu D, Akerkar S, Cuéllar J, Chambers JJ, O’Connell R, Muruganandam G, Loris R, Touma C, Kanhema T, Hayashi Y, Stratton MM, Valpuesta JM, Kursula P, Martinez A and Bramham CR  (2020). Arc self-association and formation of virus-like capsids are mediated by an N-terminal helical coil motif. The FEBS Journal. https://doi.org/10.1111/febs.15618

Zhang, H. and Bramham, C.R. (2020) Arc function in long-term synaptic plasticity: emerging mechanisms and unresolved issues. Eur J Neurosci, doi.org/10.1111/ejn.14958

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

Cassarotto, P., Girych, M., Fred, S.M., Moliner, R., Enkavi, G., Biojone, C., Cannarozzo, C., Brunello, C.A, Steinzeig, A., Winkel, F., Patil, S., Vestring, S.,  Serchov, T., Laukkanen, L., Cardon, I., Antila, H., Rog, T., Bramham, C.R., Normann, C., Lauri, S.E., Vattulainen, I., and Castrén, E.,  (2021) Antidepressants act by directly binding to TRKB neurotrophin receptors. Cell 184:1-15. 10.1016/j.cell.2021.01.034

Esvald, E.-E., Tuvikene, J., Sirp, A., Patil, S., Bramham, C.R., & Timmusk, T. (2020) CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons. J. Neurosci., 40(7):1405-1426. doi.org/10.1523/JNEUROSCI.0367-19.2019.

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

Patil, S., Chalkiadaki, K., Mergiya, T.F, Krimbacher, K., Amorim, I.S., Akerkar, S., Gkogkas, C.G., and Bramham, C.R. (2023) eIF4E phosphorylation recruits β-catenin to mRNA cap and promotes Wnt pathway translation in dentate gyrus LTP maintenance. iScience, 26(5), 106649. doi.org/10.1016/j.isci.2023.106649

Chalkiadaki, K., Kouloulia, S., Bramham, C.R., and Gkogkas, C (2020) Regulation of protein synthesis by eIF4E in the brain. In The Oxford Handbook of Neuronal Protein Synthesis pp 1–22. 10.1093/oxfordhb/9780190686307.013.12

Taha E, Patil S, Barrera I, Proud CG, Bramham CR, Rosenblum K (2020) eEF2/eEF2K pathway in the mature dentate gyrus determines neurogenesis level and cognition. Current Biology 30:1–15. doi.org/10.1016/j.cub.2020.06.061.

Berentsen B, Patil S, Wibrand K, Goff KM, Pajak M, Simpson IT, and Bramham CR. (2020) microRNA-34a acutely regulates synaptic efficacy in the adult dentate gyrus in vivo. Molecular Neurobiology doi.org/10.1007/s12035-019-01816-1

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

Berentsen B, Patil S, Wibrand K, Goff KM, Pajak M, Simpson IT, and Bramham CR. (2020) microRNA-34a acutely regulates synaptic efficacy in the adult dentate gyrus in vivo. Molecular Neurobiology doi.org/10.1007/s12035-019-01816-1

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:

 

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1991

See a complete overview of publications in Cristin.

Projects
  • 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 currently funded projects:t

The Impact of Cytoplasmic Polyadenylation on Local Translation in Neurons. EEA grant for Poland-Norway Research Cooperation. 2020-2024.

Mohn Research Center for Plasticity and Neural Circuit Dynamics in the Brain. Supported by the Trond Mohn Foundation, the University of Bergen (UiB) and the Norwegian University of Science and Technology (NTNU). 2021-2026.