Center for Nanoscale Microscopy and Molecular Physiology of the Brain

Göttingen, Germany

Center for Nanoscale Microscopy and Molecular Physiology of the Brain

Göttingen, Germany
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Riedel D.,Max Planck Institute for Biophysical Chemistry | Wenzel D.,Max Planck Institute for Biophysical Chemistry | Deckers M.,University of Gottingen | Rehling P.,Max Planck Institute for Biophysical Chemistry | And 2 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

The mitochondrial inner membrane organizing system (MINOS) is a conserved large hetero-oligomeric protein complex in the mitochondrial inner membrane, crucial for the maintenance of cristae morphology. MINOS has been suggested to represent the core of an extended protein network that controls mitochondrial function and structure, and has been linked to several human diseases. The spatial arrangement of MINOS within mitochondria is ill-defined, however. Using super-resolution stimulated emission depletion (STED) microscopy and immunogold electron microscopy, we determined the distribution of three known human MINOS subunits (mitofilin, MINOS1, and CHCHD3) in mammalian cells. Super-resolution microscopy revealed that all three subunits form similar clusters within mitochondria, and that MINOS is more abundant in mitochondria around the nucleus than in peripheral mitochondria. At the submitochondrial level, mitofilin, a core MINOS subunit, is preferentially localized at cristae junctions. In primary human fibroblasts, mitofilin labeling uncovered a regularly spaced pattern of clusters arranged in parallel to the cell growth surfaces. We suggest that this array of MINOS complexes might explain the observed phenomenon of largely horizontally arranged cristae junctions that connect the inner boundary membrane to lamellar cristae. The super-resolution images demonstrate an unexpectedly high level of regularity in the nanoscale distribution of the MINOS complex in human mitochondria, supporting an integrating role of MINOS in the structural organization of the organelle.

Hassenklover T.,University of Gottingen | Hassenklover T.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain | Manzini I.,University of Gottingen | Manzini I.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain
Journal of Neuroscience | Year: 2013

Olfactory receptor neurons extend axons into the olfactory bulb, where they face the challenge to integrate into existing circuitry. The consensus view is that in vertebrates individual receptor neurons project unbranched axons into one specific glomerulus of the olfactory bulb. We report here that, strikingly different from the generally assumed wiring principle in vertebrate olfactory systems, axons of single receptor neurons of Xenopus laevis regularly bifurcate and project into more than one glomerulus. Specifically, the innervation of multiple glomeruli is present in all ontogenetic stages of this species, from the larva to the postmetamorphic frog. Also, we show that this unexpected wiring pattern is not restricted to axons of immature receptor neurons, but that it is also a feature of mature neurons of both the main and accessory olfactory system. This glomerular innervation pattern is unique among vertebrates investigated so far and represents a new olfactory wiring strategy. © 2013 the authors.

Vigano F.,Ludwig Maximilians University of Munich | Vigano F.,Institute for Stem Cell Research | Vigano F.,University of Milan | Mobius W.,Max Planck Institute for Experimental Medicine | And 6 more authors.
Nature Neuroscience | Year: 2013

To examine the role of gray and white matter niches for oligodendrocyte differentiation, we used homo-and heterotopic transplantations into the adult mouse cerebral cortex. White matter-derived cells differentiated into mature oligodendrocytes in both niches with equal efficiency, whereas gray matter-derived cells did not. Thus, white matter promotes oligodendrocyte differentiation, and cells from this niche differentiate more easily, even in the less supportive gray matter environment. 2013 Nature America, Inc. All rights reserved.

Siddiqui T.,University of British Columbia | Tari P.,University of British Columbia | Connor S.,University of British Columbia | Zhang P.,University of British Columbia | And 7 more authors.
Neuron | Year: 2013

Selective synapse development determines how complex neuronal networks in the brain are formed. Complexes of postsynaptic neuroligins and LRRTMs with presynaptic neurexins contribute widely to excitatory synapse development, and mutations in these gene families increase the risk of developing psychiatric disorders. We find that LRRTM4 has distinct presynaptic binding partners, heparan sulfate proteoglycans (HSPGs). HSPGs are required to mediate the synaptogenic activity of LRRTM4. LRRTM4 shows highly selective expression in the brain. Within the hippocampus, we detected LRRTM4 specifically at excitatory postsynaptic sites on dentate gyrus granule cells. LRRTM4-/- dentate gyrus granule cells, but not CA1 pyramidal cells, exhibit reductions in excitatory synapse density and function. Furthermore, LRRTM4-/- dentate gyrus granule cells show impaired activity-regulated AMPA receptor trafficking. These results identifying cell-type-specific functions and multiple presynaptic binding partners for different LRRTM family members reveal an unexpected complexity in the design and function of synapse-organizing proteins

Kono Y.,Jikei University School of Medicine | Hulsmann S.,University of Gottingen | Hulsmann S.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain
Neuroscience | Year: 2016

Glycinergic neurons provide an important mechanism to control excitation of motoneurons in the brainstem and a reduction or loss of glycinergic inhibition can be deleterious by leading to hyperexcitation such as in hyperekplexia or neurodegeneration and neuronal death as in amyotrophic lateral sclerosis (ALS). Second messenger systems that change cyclic AMP and lead to phosphorylation of the α3 subunit of the glycine receptor (GlyR α3) have been shown to be potent modulators of synaptic inhibition in the spinal cord and brain stem. In this study we analyzed the role of GlyR α3 in synaptic inhibition to the hypoglossal nucleus using Glra3 (the gene encoding the glycine receptor α3 subunit) knockout mice. We observed that baseline glycinergic synaptic transmission to nucleus of hypoglossal motoneurons is rather normal in Glra3 knockout mice. Interestingly, we found that the modulation of synaptic transmission by cAMP-mediated pathways appeared to be reduced in Glra3 knockout mice. In the second postnatal week the forskolin-induced increase of miniature inhibitory postsynaptic potential (mIPSC) frequency was significantly larger in control as compared to Glra3 knockout mice suggesting that presynaptic glycine release in the hypoglossal nucleus is partially depending on GlyR α3. © 2016 IBRO.

Snaidero N.,Max Planck Institute for Experimental Medicine | Snaidero N.,University of Gottingen | Mobius W.,Max Planck Institute for Experimental Medicine | Mobius W.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain | And 12 more authors.
Cell | Year: 2014

Central nervous system myelin is a multilayered membrane sheath generated by oligodendrocytes for rapid impulse propagation. However, the underlying mechanisms of myelin wrapping have remained unclear. Using an integrative approach of live imaging, electron microscopy, and genetics, we show that new myelin membranes are incorporated adjacent to the axon at the innermost tongue. Simultaneously, newly formed layers extend laterally, ultimately leading to the formation of a set of closely apposed paranodal loops. An elaborated system of cytoplasmic channels within the growing myelin sheath enables membrane trafficking to the leading edge. Most of these channels close with ongoing development but can be reopened in adults by experimentally raising phosphatidylinositol-(3,4,5)-triphosphate levels, which reinitiates myelin growth. Our model can explain assembly of myelin as a multilayered structure, abnormal myelin outfoldings in neurological disease, and plasticity of myelin biogenesis observed in adult life. PaperFlick © 2014 Elsevier Inc.

Willig K.I.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain | Willig K.I.,Max Planck Institute for Biophysical Chemistry | Barrantes F.J.,CONICET
Current Opinion in Chemical Biology | Year: 2014

Chemical synapses in brain are structural differentiations where excitatory or inhibitory signals are vectorially transmitted between two neurons. Excitatory synapses occur mostly on dendritic spines, submicron sized protrusions of the neuronal dendritic arborizations. Axons establish contacts with these tiny specializations purported to be the smallest functional processing units in the central nervous system. The minute size of synapses and their macromolecular constituents creates an inherent difficulty for imaging but makes them an ideal object for superresolution microscopy. Here we discuss some representative examples of nanoscopy studies, ranging from quantification of receptors and scaffolding proteins in postsynaptic densities and their dynamic behavior, to imaging of synaptic vesicle proteins and dendritic spines in living neurons or even live animals. © 2014 Elsevier Ltd.

Koch J.C.,University of Gottingen | Lingor P.,University of Gottingen | Lingor P.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain
Experimental Eye Research | Year: 2016

Different pathological conditions including glaucoma, optic neuritis, hereditary optic atrophy and traumatic injury lead to a degeneration of retinal ganglion cell axons in the optic nerve. Besides this clinical relevance, several experimental models employ the optic nerve as a model system to examine general mechanisms of axonal degeneration in the central nervous system.Several experimental studies have demonstrated that an activation of autophagy is a prominent feature of axonal degeneration in the optic nerve independent of the underlying pathological condition. However, the function of autophagy in axonal degeneration remains still unclear. Inhibition of autophagy was found to attenuate axonal degeneration within the first hours after optic nerve lesion. Other studies focusing on survival of retinal ganglion cells at later postlesional time points report contradicting results, where both inhibition and induction of autophagy were beneficial for survival, depending on the model system or examination time. Therefore, a more precise understanding of the role and the kinetics of autophagy in axonal degeneration is mandatory to develop new therapies for diseases of the optic nerve.Here, we review the literature on the pathophysiological role of autophagy in axonal degeneration in the optic nerve and discuss its implications for future therapeutic approaches in diseases of the eye and the central nervous system involving axonal degeneration. © 2015 Elsevier Ltd.

Wilts B.D.,University of Gottingen | Schaap I.A.T.,University of Gottingen | Schaap I.A.T.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain | Schmidt C.F.,University of Gottingen
Biophysical Journal | Year: 2015

Cowpea chlorotic mottle virus (CCMV) forms highly elastic icosahedral protein capsids that undergo a characteristic swelling transition when the pH is raised from 5 to 7. Here, we performed nano-indentation experiments using an atomic force microscope to track capsid swelling and measure the shells' Young's modulus at the same time. When we chelated Ca2+ ions and raised the pH, we observed a gradual swelling of the RNA-filled capsids accompanied by a softening of the shell. Control experiments with empty wild-type virus and a salt-stable mutant revealed that the softening was not strictly coupled to the swelling of the protein shells. Our data suggest that a pH increase and Ca2+ chelation lead primarily to a loosening of contacts within the protein shell, resulting in a softening of the capsid. This appears to render the shell metastable and make swelling possible when repulsive forces among the capsid proteins become large enough, which is known to be followed by capsid disassembly at even higher pH. Thus, softening and swelling are likely to play a role during inoculation. © 2015 Biophysical Society.

Balasubramanian G.,Max Planck Institute for Biophysical Chemistry | Balasubramanian G.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain | Lazariev A.,Max Planck Institute for Biophysical Chemistry | Arumugam S.R.,Max Planck Institute for Biophysical Chemistry | Duan D.-W.,Max Planck Institute for Biophysical Chemistry
Current Opinion in Chemical Biology | Year: 2014

Nitrogen-Vacancy (NV) color center in diamond is a flourishing research area that, in recent years, has displayed remarkable progress. The system offers great potential for realizing futuristic applications in nanoscience, benefiting a range of fields from bioimaging to quantum-sensing. The ability to image single NV color centers in a nanodiamond and manipulate NV electron spin optically under ambient condition is the main driving force behind developments in nanoscale sensing and novel imaging techniques. In this article we discuss current status on the applications of fluorescent nanodiamonds (FND) for optical super resolution nanoscopy, magneto-optical (spin-assisted) sub-wavelength localization and imaging. We present emerging applications such as single molecule spin imaging, nanoscale imaging of biomagnetic fields, sensing molecular fluctuations and temperatures in live cellular environments. We summarize other current advances and future prospects of NV diamond for imaging and sensing pertaining to bio-medical applications. © 2014 Elsevier Ltd.

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