Dr. Corette J. Wierenga
Faculty of Science, Utrecht University
Kruytgebouw, room N511
3584 CH Utrecht
Tel. +31-(0)30-253 2659
Fax +31-(0)30-253 3655
Corette Wierenga studied physics at the VU University Amsterdam and received her PhD in neurobiology at the University of Amsterdam in 2002. She worked as a postdoctoral fellow in the laboratory of Dr. Gina Turrigano at Brandeis University in Waltham (MA), USA (2002-2006) and with Prof. Tobias Bonhoeffer at the Max Planck Institute of Neurobiology in Martinsried, Germany (2006-2011). In 2011 she joined the Division of Cell Biology at the Department of Biology at Utrecht University, where she started an independent research group since 2012, supported by an NWO Vernieuwingsimpuls VIDI award. She became Associate Professor in 2015.
Our brain consists of millions of neurons, interconnected through synaptic connections. Synapses are not static, but highly dynamic structures which respond to experience by continuously adjusting their strength and number. When neuronal circuits adapt during development and learning, synaptic connections are adjusted. In a healthy brain, changes in excitatory and inhibitory synapses are coordinated to assure neuronal and network function, but the cellular mechanisms of this synaptic coordination is not well understood. Synaptic dysfunction and distortion of coordination between excitatory and inhibitory synapses are at the basis of many neurodevelopmental and neurological disorders, including autism and early stages of Alzheimer’s disease.
We previously found that new inhibitory synapses are generated by the appearance of new boutons at locations where inhibitory axons are in close contact with dendrites. Our live imaging data shows that inhibitory synapses are highly dynamic structures, appearing, disappearing and reappearing on a time scale of tens of minutes. These dynamics facilitate rapid adjustments of inhibitory axons in response to activity or other environmental signals.
We are using two-photon microscopy to visualize inhibitory and excitatory synapses, axons and dendrites in hippocampal organotypic cultures and acute slices. Two-photon microscopy has the advantage of producing high resolution (< 1 μm) images with minimal photo damage, allowing repeated imaging of small subcellular structures in intact tissue. We combine live imaging with electrophysiology and molecular techniques to manipulate or label specific proteins and/or cell types.
We study the molecular processes underlying inhibitory synapse formation and plasticity, with a special emphasis on interactions with excitatory synapses within dendrites. We use our fundamental knowledge on synaptic plasticity and brain development to collaborate with clinical and industrial partners to improve the neurobiological understanding of brain disorders.
|Cátia Perreiras-Frias (together with C. Hoogenraad)|
|Hai Yin Hu|
|Elske Bijvank (together with Louk Vanderschuren from UU Veterinary Medicine)|
|Matthijs van Kesteren|
Frias CP, Bresser T, Scheefhals L, van Bergen en Henegouwen PMP, Hoogenraad CC, Wierenga CJ (2017) Molecular pathway underlying bouton stabilization by Semaphorin4D during inhibitory synapse formation. BioRxiv 100271; doi: https://doi.org/10.1101/100271
Müllner F, Wierenga CJ*, Bonhoeffer T* (2015) Precision of inhibition: Dendritic inhibition by individual GABAergic synapses on hippocampal pyramidal cells is confined in space and time. Neuron 87, 576-589. * equal contributions
Schuemann A, Klawiter A, Bonhoeffer T, Wierenga CJ (2013) Structural plasticity of GABAergic axons is regulated by network activity and GABAA receptor activation. Frontiers in Neural Circuits 7: 113.
Keck T, Scheuss V, Jacobsen RI, Wierenga CJ, Eysel UT, Bonhoeffer T, Hübener M. Loss of sensory input causes rapid structural changes of inhibitory neurons in adult mouse visual cortex. Neuron. 2011 Sep 8; 71(5):869-82.
Wierenga CJ, Müllner FE, Rinke I, Keck T, Stein V, Bonhoeffer T. Molecular and electrophysiological characterization of GFP-expressing CA1 interneurons in GAD65-GFP mice. PLoS One. 2010 Dec 31; 5(12):e15915.
Wierenga CJ, Becker N, Bonhoeffer T. GABAergic synapses are formed without the involvement of dendritic protrusions. Nat Neurosci. 2008 Sep; 11(9):1044-52.
Wierenga CJ (2017) Live imaging of inhibitory axons: Synapse formation as a dynamic trial-and-error process. Brain Research Bulletin 127: 43-49.
Frias CP, Wierenga CJ (2013) Activity-dependent adaptations in inhibitory axons. Frontiers in Cellular Neuroscience 7: 219.
Vogels TP, Froemke RC, Doyon N, Gilson M, Haas JS, Liu R, Maffei A, Miller P, Wierenga CJ, Woodin MA, Zenke F and Sprekeler H (2013) Inhibitory synaptic plasticity: spike timing-dependence and putative network function. Frontiers in Neural Circuits 7: 119.
Harschnitz O, van den Berg LH, Johansen LE, Jansen MD, Kling S, Vieira De Sá R, Vlam L, van Rheenen W, Karst H, Wierenga CJ, Pasterkamp RJ, van der Pol WL (2016) Autoantibody pathogenicity in a multifocal motor neuropathy iPSC-derived model. Annals of Neurology 80: 71-88.
Kellner Y, Fricke S, Kramer S, Iobbi C, Wierenga CJ, Schwab ME, Korte M, Zagrebelsky M (2016) Nogo-A controls structural plasticity at dendritic spines by rapidly modulating actin dynamics. Hippocampus 26: 816-831.
Lenz M, Galanis C, Müller-Dahlhaus F, Opitz A, Wierenga CJ, Szabó G, Ziemann U, Deller T, Klaus Funke, and Vlachos A (2015) Repetitive magnetic stimulation induces plasticity of inhibitory synapses. Nature Communications 7: 10020.
Esteves da Silva M, Adrian M, Schätzle P, Lipka J, Watanabe T, Cho S, Futai K, Wierenga CJ, Kapitein LC, Hoogenraad CC (2015) Positioning of AMPA receptor-containing endosomes regulates synapse architecture. Cell Reports 13: 933-943.
Gomis-Rüth S, Stiess M, Wierenga CJ, Meyn L, Bradke F (2014) Single cell axotomy of cultured hippocampal neurons integrated in neuronal circuits. Nature Protocols 9: 1028-1037.