Neural extracellular matrix regulates visual sensory motor integration

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

SUMMARY Visual processing depends on sensitive and balanced synaptic neurotransmission. Extracellular matrix proteins in the environment of cells are key modulators in synaptogenesis and synaptic plasticity. In the present study, we provide evidence that the combined loss of the four extracellular matrix components brevican, neurocan, tenascin-C and tenascin-R in quadruple knockout mice leads to severe retinal dysfunction and diminished visual motion processing in vivo . Remarkably, impaired visual motion processing was accompanied by a developmental loss of cholinergic direction-selective starburst amacrine cells. Additionally, we noted imbalance of inhibitory and excitatory synaptic signaling in the quadruple knockout retina. Collectively, the study offers novel insights into the functional importance of four key extracellular matrix proteins for retinal function, visual motion processing and synaptic integrity. Graphical Abstract In brief In their study, Reinhard et al. show that the combined loss of the extracellular matrix components brevican, neurocan, tenascin-C and tenascin-R in quadruple knockout mice leads to retinal dysfunction, diminished visual motion processing, developmental loss of cholinergic direction-selective starburst amacrine cells and imbalance of inhibitory and excitatory synaptic integrity. Highlights Combined loss of the four extracellular matrix molecules brevican, neurocan, tenascin-C and tenascin-R causes retinal dysfunction Impaired visual motion processing in quadruple, tenascin-C and tenascin-R knockout mice Loss of cholinergic direction-selective starburst amacrine cells in the quadruple knockout retina The matrisome influences inhibitory and excitatory synaptic balance

Authors 12

1. Jacqueline Reinhard corresponding

   Ruhr University Bochum

   Affiliation as printed

   Department of Cell Morphology and Molecular Neurobiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, 44780 Bochum, Germany

2. Cornelius Mueller-Buehl

   Ruhr University Bochum

   Affiliation as printed

   Department of Cell Morphology and Molecular Neurobiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, 44780 Bochum, Germany

3. Susanne Wiemann

   Ruhr University Bochum

   Affiliation as printed

   Department of Cell Morphology and Molecular Neurobiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, 44780 Bochum, Germany

4. Lars Roll

   Ruhr University Bochum

   Affiliation as printed

   Department of Cell Morphology and Molecular Neurobiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, 44780 Bochum, Germany

5. Veronika Luft

   Ruhr University Bochum

   Affiliation as printed

   Department of Cell Morphology and Molecular Neurobiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, 44780 Bochum, Germany

6. Hamed Shabani

   University of Tübingen

   Affiliation as printed

   Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard-Karls-University Tuebingen, 72076 Tuebingen, Germany

   Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard-Karls-University Tuebingen, 7076 Tuebingen, Germany

7. Daniel L. Rathbun

   University of Tübingen

   Affiliation as printed

   Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard-Karls-University Tuebingen, 72076 Tuebingen, Germany

   Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard-Karls-University Tuebingen, 7076 Tuebingen, Germany

8. Lin Gan Aachen Interdisciplinary Centre for Clinical Research Aachen

   RWTH Aachen University

   Affiliation as printed

   Interdisciplinary Centre for Clinical Research Aachen, RWTH Aachen University, 52074 Aachen, Germany

9. Chao‐Chung Kuo Aachen Interdisciplinary Centre for Clinical Research Aachen

   RWTH Aachen University

   Affiliation as printed

   Interdisciplinary Centre for Clinical Research Aachen, RWTH Aachen University, 52074 Aachen, Germany

10. Julia Franzen Aachen Interdisciplinary Centre for Clinical Research Aachen

    RWTH Aachen University

    Affiliation as printed

    Interdisciplinary Centre for Clinical Research Aachen, RWTH Aachen University, 52074 Aachen, Germany

11. Stephanie Carolin Joachim

    Ruhr University Bochum · University Hospitals of the Ruhr-University of Bochum

    Affiliation as printed

    Experimental Eye Research Institute, University Eye Hospital, Ruhr University Bochum, 44892 Bochum, Germany

    Experimental Eye Research Institute, University Eye Hospital, Ruhr University Bochum, 892 Bochum, Germany

12. Andréas Faissner corresponding

    Ruhr University Bochum

    Affiliation as printed

    Department of Cell Morphology and Molecular Neurobiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, 44780 Bochum, Germany