Research Group Presynaptic Plasticity

The function of our brains is based on information transmission, processing and storage by neuronal networks, which are composed of billions neuronal cells, neurons. These neurons communicate with each other at specialized contact sites named synapses. Here the incoming electric signal induces a release of neurotransmitter from the upstream cell, which can be detected and converted in an electrical signal in the downstream cell. The synaptic signal transmission is highly elaborate and precisely regulated process and any disturbance of it leads to brain malfunctions such as epilepsy and neuropsychiatric or neurodegenerative diseases. The usage-dependent modification in the synaptic transmission – referred to as synaptic plasticity – resembles one crucial cellular mechanism for learning and memory formation.

The Research group Presynaptic Plasticity investigates the molecular mechanisms of presynaptic function and dysfunction. In the presynaptic bouton, complex molecular machinery works in a precisely orchestrated manner to ensure fast and precise neurotransmitter release. The molecular identity of most components of the presynaptic release machinery was established in past decade. However, we still do not completely understand, how the dynamic molecular interactions implement presynaptic performance and which mechanisms are engaged in modulation of this complex ensemble in order to execute functional plasticity of neurotransmitter release. This knowledge is indispensable to link functional characterization of presynaptic specializations with their molecular and structural mapping, which is in turn instrumental for rational design of pharmacological and genetic interventions applicable in rain diseases involving brake-down of synaptic function.

  • Head

    Head

    Anna Fejtova graduated at the Charles University in Prague, Czech Republic. She obtained her PhD in Neuroscience at the Neuroscience Center Zurich and Dr.sc.nat. at University of Zurich. She moved to Leibniz Institute for Neurobiology as a fellow of Swiss National Science Foundation in the department of Eckart Gundelfinger in 2003. She stayed in his department as scientist and later on as group leader to become leader of the independent Reserch Group Presynaptic Plasticity in 2013.

    Since 2016 she also heads Laboratory for Molecular Neurobiology and Neurophotonics at Department of Psychiatry and Psychotherapy, University Hospital Erlangen, where she is appointed as university professor for Molecular Psychiatry.

  • Members

    Members

    Head  
    Prof. Dr. Anna Fejtova+49 9131 85-46155anna.fejtova@lin-magdeburg.de
    PhD student  
    Debarpan Guhathakurta+49 9131 85-44886 
    Lab assistent  
    Janina Juhle+49-391-6263- 93281janina.juhle@lin-magdeburg.de

     

  • Projects

    Projects

    In our current research we follow two main lines of investigations:

    First, we study molecular mechanisms behind presynaptic short-term plasticity. These rely on dynamic regulations of neurotransmitter release, occur in frames of seconds to minutes and are mediated by synapse-autonomous mechanisms, such as phosphorylation or ubiquitination of synaptic proteins.

    Second, we investigate mechanisms of long-term changes in presynaptic function corresponding to physiological phenomena like long-term potentiation, depression or homeostatic scaling. Here we mainly focus on presynapse-to-nucleus signalling driving eventually neuronal activity-driven reconfiguration of gene expressional programs, which is required to convert transient presynaptic modifications to more persistent molecular, structural and functional remodelling.

    To learn more about the projects of the group navigate to www.fejtovalab.com.

  • Third Party Funds

    Third Party Funds

    2008-2019
    DFG SFB 779 Neurobiologie motiverten Verhaltens

    Beeinflussung der Exzitations/Inhibitionsbalance durch NMDA Rezeptorantagonsiten bei Depression
    http://www.sfb779.de/a06.html

     

    2017-2020       
    DFG GRK2162
    Neurodevelopment and Vulnerability of the Central Nervous System
    https://www.grk2162.med.fau.de/

     

    2016-2019       
    BMBF Generare
    German Network of RASopathy Research
    http://www.generare.de/

     

    2019-2022       
    BMBF Generare2
    German Network of RASopathy Research
    http://www.generare.de/

  • Publications

    Publications

    2019

    Schattling B, Engler JB, Volkmann C, Rothammer N, Woo MS, Petersen M, Winkler I, Kaufmann M, Rosenkranz SC, Fejtova A, Thomas U, Bose A, Bauer S, Träger S, Miller KK, Brück W, Duncan KE, Salinas G, Soba P, Gundelfinger ED, Merkler D, Friese MA. 2019. Bassoon proteinopathy drives neurodegeneration in multiple sclerosis. Nature Neuroscience. https://doi.org/10.1038/s41593-019-0385-4

     

    2018

    Lazarevic V, Yang Y, Ivanova D, Fejtova A, Svenningsson P. 2018. Riluzole attenuates the efficacy of glutamatergic transmission by interfering with the size of the readily releasable neurotransmitter pool. Neuropharmacology. 143:38-48. https://doi.org/10.1016/j.neuropharm.2018.09.021

    Li M, Woelfer M, Colic L, Safron A, Chang C, Heinze HJ, Speck O, Mayberg HS, Biswal BB, Salvadore G, Fejtova A, Walter M. 2018. Default mode network connectivity change corresponds to ketamine’s delayed glutamatergic effects. European Archives of Psychiatry and Clinical Neuroscience. https://doi.org/10.1007/s00406-018-0942-y

    Annamneedi A, Caliskan G, Müller S, Montag D, Budinger E, Angenstein F, Fejtova A, Tischmeyer W, Gundelfinger ED, Stork O. 2018. Ablation of the presynaptic organizer Bassoon in excitatory neurons retards dentate gyrus maturation and enhances learning performance. Brain Structure and Function. 223(7):3423-3445. https://doi.org/10.1007/s00429-018-1692-3

     

    2017

    Schweitzer B, Singh J, Fejtova A, Groc L, Heine M, Frischknecht R. 2017. Hyaluronic acid based extracellular matrix regulates surface expression of GluN2B containing NMDA receptors. Scientific Reports. 7(1). https://doi.org/10.1038/s41598-017-07003-3

    Lazarevic V, Fieńko S, Andres-Alonso M, Anni D, Ivanova D, Montenegro-Venegas C, Gundelfinger ED, Cousin MA, Fejtova A. 2017. Physiological concentrations of amyloid beta regulate recycling of synaptic vesicles via alpha7 acetylcholine receptor and CDK5/calcineurin signaling. Frontiers in Molecular Neuroscience. 10. https://doi.org/10.3389/fnmol.2017.00221

    Li M, Demenescu LR, Colic L, Metzger CD, Heinze HJ, Steiner J, Speck O, Fejtova A, Salvadore G, Walter M. 2017. Temporal Dynamics of Antidepressant Ketamine Effects on Glutamine Cycling Follow Regional Fingerprints of AMPA and NMDA Receptor Densities. Neuropsychopharmacology. 42(6):1201-1209. https://doi.org/10.1038/npp.2016.184

    Kawabe H, Mitkovski M, Kaeser PS, Hirrlinger J, Opazo F, Nestvogel D, Kalla S, Fejtova A, Verrier SE, Bungers SR, Cooper BH, Varoqueaux F, Wang Y, Nehring RB, Gundelfinger ED, Rosenmund C, Rizzoli SO, Südhof TC, Rhee J-S, Brose N. 2017. ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones. Journal of Cell Biology. 216(4):1143-1161. https://doi.org/10.1083/jcb.201606086

    Altmüller F, Pothula S, Annamneedi A, Nakhei-Rad S, Montenegro-Venegas C, Pina-Fernández E, Marini C, Santos M, Schanze D, Montag D, Ahmadian MR, Stork O, Zenker M, Fejtova A. 2017. Aberrant neuronal activity-induced signaling and gene expression in a mouse model of RASopathy. PLoS Genetics. 13(3). https://doi.org/10.1371/journal.pgen.1006684

     

    2016

    Ivanova D, Dirks A, Fejtova A. 2016. Bassoon and piccolo regulate ubiquitination and link presynaptic molecular dynamics with activity-regulated gene expression. Journal of Physiology. 594(19):5441-5448. https://doi.org/10.1113/JP271826

     

    2015

    Ivanova D, Dirks A, Montenegro-Venegas C, Schöne C, Altrock WD, Marini C, Frischknecht R, Schanze D, Zenker M, Gundelfinger ED, Fejtova A. 2015. Synaptic activity controls localization and function of CtBP1 via binding to Bassoon and Piccolo. EMBO Journal. 34(8):1056-1077. https://doi.org/10.15252/embj.201488796

     

    2014

    Morelli E, Ghiglieri V, Pendolino V, Bagetta V, Pignataro A, Fejtova A, Costa C, Ammassari-Teule M, Gundelfinger ED, Picconi B, Calabresi P. 2014. Environmental enrichment restores CA1 hippocampal LTP and reduces severity of seizures in epileptic mice. Experimental Neurology. 261:320-327. https://doi.org/10.1016/j.expneurol.2014.05.010

    Davydova D, Marini C, King C, Klueva J, Bischof F, Romorini S, Montenegro-Venegas C, Heine M, Schneider R, Schroeder M, Altrock WD, Henneberger C, Rusakov DA, Gundelfinger ED, Fejtova A. 2014. Bassoon specifically controls presynaptic P/Q-type Ca2+ channels via RIM-binding protein. Neuron. 82(1):181-194. https://doi.org/10.1016/j.neuron.2014.02.012

     

    2013

    Lazarevic V, Pothula S, Andres-Alonso M, Fejtova A. 2013. Molecular mechanisms driving homeostatic plasticity of neurotransmitter release. Frontiers in Cellular Neuroscience. 7(DEC). https://doi.org/10.3389/fncel.2013.00244

    Regus-Leidig H, Ott C, Löhner M, Atorf J, Fuchs M, Sedmak T, Kremers J, Fejtová A, Gundelfinger ED, Brandstätter JH. 2013. Identification and Immunocytochemical Characterization of Piccolino, a Novel Piccolo Splice Variant Selectively Expressed at Sensory Ribbon Synapses of the Eye and Ear. PLoS ONE. 8(8):e70373. https://doi.org/10.1371/journal.pone.0070373

    Waites CL, Leal-Ortiz SA, Okerlund N, Dalke H, Fejtova A, Altrock WD, Gundelfinger ED, Garner CC. 2013. Bassoon and Piccolo maintain synapse integrity by regulating protein ubiquitination and degradation. EMBO Journal. 32(7):954-969. https://doi.org/10.1038/emboj.2013.27

    Schroeder M, Stellmacher A, Romorini S, Marini C, Montenegro-Venegas C, Altrock WD, Gundelfinger ED, Fejtova A. 2013. Regulation of Presynaptic Anchoring of the Scaffold Protein Bassoon by Phosphorylation-Dependent Interaction with 14-3-3 Adaptor Proteins. PLoS ONE. 8(3):e58814. https://doi.org/10.1371/journal.pone.0058814

    Jing Z, Rutherford MA, Takago H, Frank T, Fejtova A, Khimich D, Moser T, Strenzke N. 2013. Disruption of the presynaptic cytomatrix protein bassoon degrades ribbon anchorage, multiquantal release, and sound encoding at the hair cell afferent synapse. Journal of Neuroscience. 33(10):4456-4467. https://doi.org/10.1523/JNEUROSCI.3491-12.2013

     

    2012

    Maas C, Torres VI, Altrock WD, Leal-Ortiz S, Wagh D, Terry-Lorenzo RT, Fejtova A, Gundelfinger ED, Ziv NE, Garner CC. 2012. Formation of Golgi-derived active zone precursor vesicles. Journal of Neuroscience. 32(32):11095-11108. https://doi.org/10.1523/JNEUROSCI.0195-12.2012

    Hübler D, Rankovic M, Richter K, Lazarevic V, Altrock WD, Fischer KD, Gundelfinger ED, Fejtova A. 2012. Differential spatial expression and subcellular localization of CtBP family members in Rodent Brain. PLoS ONE. 7(6):e39710. https://doi.org/10.1371/journal.pone.0039710

    Gundelfinger ED, Fejtova A. 2012. Molecular organization and plasticity of the cytomatrix at the active zone. Current Opinion in Neurobiology. 22(3):423-430. https://doi.org/10.1016/j.conb.2011.10.005

     

    2011

    Lazarevic V, Schöne C, Heine M, Gundelfinger ED, Fejtova A. 2011. Extensive remodeling of the presynaptic cytomatrix upon homeostatic adaptation to network activity silencing. Journal of Neuroscience. 31(28):10189-10200. https://doi.org/10.1523/JNEUROSCI.2088-11.2011

     

    2010

    Frank T, Rutherford MA, Strenzke N, Neef A, Pangršič T, Khimich D, Fejtová A, Gundelfinger ED, Liberman MC, Harke B, Bryan KE, Lee A, Egner A, Riedel D, Moser T. 2010. Bassoon and the synaptic ribbon organize Ca2+ channels and vesicles to add release sites and promote refilling. Neuron. 68(4):724-738. https://doi.org/10.1016/j.neuron.2010.10.027

    Fejtova A, Schmidt H, Weyhersmüller A, Silver RA, Gundelfinger ED, Eilers J. 2010. Bassoon speeds vesicle reloading at a central excitatory synapse. Neuron. 68(4):710-723. https://doi.org/10.1016/j.neuron.2010.10.026

    Lanore F, Blanchet C, Fejtova A, Pinheiro P, Richter K, Balschun D, Gundelfinger E, Mulle C. 2010. Impaired development of hippocampal mossy fibre synapses in mouse mutants for the presynaptic scaffold protein Bassoon. Journal of Physiology. 588(12):2133-2145. https://doi.org/10.1113/jphysiol.2009.184929

    Ghiglieri V, Sgobio C, Patassini S, Bagetta V, Fejtova A, Giampá C, Marinucci S, Heyden A, Gundelfinger ED, Fusco FR, Calabresi P, Picconi B. 2010. TrkB/BDNF-dependent striatal plasticity and behavior in a genetic model of epilepsy: Modulation by valproic acid. Neuropsychopharmacology. 35(7):1531-1540. https://doi.org/10.1038/npp.2010.23

     

    2009

    Gundelfinger ED, Fejtová A. 2009. Neurotransmitter release: a docking role for UNC-13 proteins (Commentary on Siksou et al.). European Journal of Neuroscience. 30(1):47-48. https://doi.org/10.1111/j.1460-9568.2009.06832.x

    Fejtova A, Davydova D, Bischof F, Lazarevic V, Altrock WD, Romorini S, Schöne C, Zuschratter W, Kreutz MR, Garner CC, Ziv NE, Gundelfinger ED. 2009. Dynein light chain regulates axonal trafficking and synaptic levels of Bassoon. Journal of Cell Biology. 185(2):341-355. https://doi.org/10.1083/jcb.200807155

    Gundelfinger ED, Altrock WD, Fejtová A. 2009. Active zone. Binder MD, Hirokawa N, Windhorst U, Hrsg. in Encyclopedia of Neuroscience. Berlin, Heidelberg: Springer. S. 44-49.

     

    2008

    Spiwoks-Becker I, Maus C, Tom Dieck S, Fejtová A, Engel L, Wolloscheck T, Wolfrum U, Vollrath L, Spessert R. 2008. Active zone proteins are dynamically associated with synaptic ribbons in rat pinealocytes. Cell and Tissue Research. 333(2):185-195. https://doi.org/10.1007/s00441-008-0627-3

    Frischknecht R, Fejtova A, Viesti M, Stephan A, Sonderegger P. 2008. Activity-induced synaptic capture and exocytosis of the neuronal serine protease neurotrypsin. Journal of Neuroscience. 28(7):1568-1579. https://doi.org/10.1523/JNEUROSCI.3398-07.2008

     

    2007

    Siksou L, Rostaing P, Lechaire JP, Boudier T, Ohtsuka T, Fejtová A, Kao HT, Greengard P, Gundelfinger ED, Triller A, Marty S. 2007. Three-dimensional architecture of presynaptic terminal cytomatrix. Journal of Neuroscience. 27(26):6868-6877. https://doi.org/10.1523/JNEUROSCI.1773-07.2007

     

    2006

    Dresbach T, Fejtová A, Gundelfinger ED. 2006. Assembly of presynaptic active zones. in Molecular Mechanisms of Synaptogenesis. S. 235-245. https://doi.org/10.1007/978-0-387-32562-0_17

    Fejtova A, Gundelfinger ED. 2006. Molecular organization and assembly of the presynaptic active zone of neurotransmitter release. Results and Problems in Cell Differentiation. 43:49-68. https://doi.org/10.1007/400_012

     

    2005

    Tom Dieck S, Altrock WD, Kessels MM, Qualmann B, Regus H, Brauner D, Fejtová A, Bracko O, Gundelfinger ED, Brandstätter JH. 2005. Molecular dissection of the photoreceptor ribbon synapse: Physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex. Journal of Cell Biology. 168(5):825-836. https://doi.org/10.1083/jcb.200408157

     

    2002

    Mannová P, Liebl D, Krauzewicz N, Fejtová A, Štokrová J, Palková Z, Griffin BE, Forstová J. 2002. Analysis of mouse polyomavirus mutants with lesions in the minor capsid proteins. Journal of General Virology. 83(9):2309-2319. https://doi.org/10.1099/0022-1317-83-9-2309

     

    Please find all publication also here: https://www.ncbi.nlm.nih.gov/pubmed/?term=fejtova+anna

  • Hugo Junkers Award

    Hugo Junkers Award

    Anna Fejtová´team was happy about the third place at the Hugo-Junkers-Prize 2015. They were working on the protein CtBP1, an "activity switch" in nerve cells. Studies have shown that CtBP1 is a signalling mediator between the cell nucleus and the synapses of a nerve cell and plays an important role in learning and memory formation.

    It also has an effect on the pathological activity of the brain. For example, the scientists were able to show why a change in diet, the so-called ketogenic diet, reduces the typical symptoms of epilepsy patients. Since this diet also influences the course of other brain disorders, the Magdeburg scientists are now investigating the function of this signaling pathway in other neuropsychiatric and neurodegenerative diseases such as depression.

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