Research group: Neuron-glia interactions and extracellular matrix post-strokeNeuron-glia interactions play a pivotal role in the regulation of homeostasis and plasticity of neural networks. Although previously glial cells were thought to be merely a supportive element, today they are known to participate in many aspects of neuronal excitation, outgrowth and survival. A significant part of glial functions relies on extracellular matrix (ECM) production. Depending on how the extracellular environment is shaped, brain networks can become more rigid or more plastic. When this subtle regulation is affected under pathological conditions, the restorative processes may be compromised, leading to brain injuries. On the other hand, by understanding of how neurons, glial cells and extracellular matrix play together in an ischemic brain, we aim to develop novel therapeutic approaches.
Our research projects at a glance:
- Reorganization of neural networks connectivity and function (Figure 1)
- Analysis of astrocyte morphology and extracellular matrix (ECM) in the ischemic brain
- Astrocytic control of neuronal synchronization in vitro (using so-called Multiple Electrode Arrays, MEA)
- Superresolution imaging of extracellular matrix (ECM) organization at nanoscale using SIM, STED and STORM microscopy (Figure 2)
Figure 1. Astrocyte-ECM-neuron interactions and neuronal plasticity. (A) The highly organized ECM restricts adult neuronal plasticity, by providing inhibitory environment (depicted in red) that restricts astrocyte-induced plasticity and by embedding repulsive guidance molecules. Within this matrix, permissive areas are left, depicted by green shading. (B) Neuronal plasticity occurs upon the loosening of ECM, favoring synaptic changes by destabilizing the inhibitory environment, releasing growth factors and enabling astrocyte-induced plasticity. (C) A mature mouse hippocampus neuron was labelled for the presynaptic synapse marker vesicular glutamate transporter-1 (VGlut1), the postsynaptic excitatory synapse marker PSD95, and the ECM marker aggrecan after 21 days in culture. The high magnification insert (C) depicts that structural synapses are predominantly formed in the dot-like ECM free areas.
Figure 2. Superresolution imaging of ECM around a single cortical neuron. Left: The meshwork of macromolecules (aggrecan in red, glycans in green) is detected with 3D Structured Illumination Microscopy (SIM). Right: Image processing algorithm identifies the vertices of the macromolecular net.
Dzyubenko E, Gottschling C, Faissner A. Neuron-Glia Interactions in Neural Plasticity: Contributions of Neural Extracellular Matrix and Perineuronal Nets. Neural Plast. 2016; 14.
Gottschling C, Dzyubenko E, Geissler M, Faissner A. The indirect neuron-astrocyte co-culture assay: an in vitro set up for the detailed investigation of neuron-glia interactions. J Vis Exp. 2016; 117.
Dzyubenko E, Juckel G, Faissner A. The antipsychotic drugs olanzapine and haloperidol modify network connectivity and spontaneous activity of neural networks in vitro. Sci Rep. 2017; 7(1): 11609.
Dzyubenko E, Rozenberg A, Hermann DM, Faissner A. Colocalization of synapse marker proteins evaluated by STED-microscopy reveals patterns of neuronal synapse distribution in vitro. J Neurosci Meth. 2017; 273: 149-159.