Max Planck Institute For Neurobiologie

Schönau am Königssee, Germany

Max Planck Institute For Neurobiologie

Schönau am Königssee, Germany
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Wekerle H.,Max Planck Institute For Neurobiologie
Rheumatology (United Kingdom) | Year: 2016

In a transgenic model of spontaneous experimental autoimmune encephalomyelitis, autoimmune attack against the CNS requires the presence of an intact commensal gut flora. Extending this observation to human autoimmune disease, such as multiple sclerosis, we postulate that the pathogenic reaction requires the coincidence of at least three factors: a permissive genetic disposition, a pro-inflammatory intestinal microbial profile, and the accumulation of autoreactive T cells in the gut-associated lymphatic tissue. This concept may offer new approaches to diagnostic markers and non-invasive therapies. © The Author 2016.

Galili D.S.,Max Planck Institute For Neurobiologie | Ludke A.,University of Konstanz | Galizia C.G.,University of Konstanz | Szyszka P.,University of Konstanz | Tanimoto H.,Max Planck Institute For Neurobiologie
Journal of Neuroscience | Year: 2011

The neural representation of a sensory stimulus evolves with time, and animals keep that representation even after stimulus cessation (i.e., a stimulus "trace"). To contrast the memories of an odor and an odor trace, we here establish a rigorous trace conditioning paradigm in the fruit fly, Drosophila melanogaster. We modify the olfactory associative learning paradigm, in which the odor and electric shock are presented with a temporal overlap (delay conditioning). Given a few-second temporal gap between the presentations of the odor and the shock in trace conditioning, the odor trace must be kept until the arrival of electric shock to form associative memory. We found that memories after trace and delay conditioning have striking similarities: both reached the same asymptotic learning level, although at different rates, and both kinds ofmemory have similar decay kinetics and highly correlated generalization profiles across odors. In search of the physiological correlate of the odor trace, we used in vivo calcium imaging to characterize the odor-evoked activity of the olfactory receptor neurons in the antennal lobe. After the offset of odor presentation, the receptor neurons showed persistent, odor-specific response patterns that lasted for a few seconds and were fundamentally different from the response patterns during the stimulation. Weak correlation between the behavioral odor generalization profile in trace conditioning and the physiological odor similarity profiles in the antennal lobe suggest that the odor trace used for associative learning may be encoded downstream of the olfactory receptor neurons. © 2011 the authors.

Nguyen Q.-T.,University of California at San Diego | Schroeder L.F.,University of California at San Diego | Mank M.,Max Planck Institute For Neurobiologie | Muller A.,University of California at San Diego | And 2 more authors.
Nature Neuroscience | Year: 2010

Tools from molecular biology, combined with in vivo optical imaging techniques, provide new mechanisms for noninvasively observing brain processes. Current approaches primarily probe cell-based variables, such as cytosolic calcium or membrane potential, but not cell-to-cell signaling. We devised cell-based neurotransmitter fluorescent engineered reporters (CNiFERs) to address this challenge and monitor in situ neurotransmitter receptor activation. CNiFERs are cultured cells that are engineered to express a chosen metabotropic receptor, use the G q protein-coupled receptor cascade to transform receptor activity into a rise in cytosolic [Ca 2+] and report [Ca 2+] with a genetically encoded fluorescent Ca 2+ sensor. The initial realization of CNiFERs detected acetylcholine release via activation of M1 muscarinic receptors. We used chronic implantation of M1-CNiFERs in frontal cortex of the adult rat to elucidate the muscarinic action of the atypical neuroleptics clozapine and olanzapine. We found that these drugs potently inhibited in situ muscarinic receptor activity. © 2010 Nature America, Inc. All rights reserved.

Aramuni G.,Max Planck Institute For Neurobiologie | Griesbeck O.,Max Planck Institute For Neurobiologie
Experimental Neurology | Year: 2013

Neuronal circuits develop, adjust to experience and degenerate in response to injury or disease in the course of weeks and months. Available recording techniques, however, typically sample physiological properties of identified neurons on the time scale of minutes and hours. Thus, in order to obtain a full understanding of a long term physiological process data need to be extrapolated from numerous experimental sessions and animals, often collected blindly and under variable conditions. The generation and ongoing engineering of genetically encoded calcium indicators creates an opportunity to repeatedly record activity from the same individual neurons in vivo over weeks, months and potentially the entire lifetime of a model organism. Chronic calcium imaging with genetically encoded indicators thus may allow to establish functional biographies of identified neuronal cell types in the brain and to reveal the physiological relevance of structural changes as they occur under natural and pathological conditions. © 2012 Elsevier Inc.

Ueno T.,Kumamoto University | Tomita J.,Kumamoto University | Tanimoto H.,Max Planck Institute For Neurobiologie | Endo K.,University of Tokyo | And 3 more authors.
Nature Neuroscience | Year: 2012

Sleep is required to maintain physiological functions, including memory, and is regulated by monoamines across species. Enhancement of dopamine signals by a mutation in the dopamine transporter (DAT) decreases sleep, but the underlying dopamine circuit responsible for this remains unknown. We found that the D1 dopamine receptor (DA1) in the dorsal fan-shaped body (dFSB) mediates the arousal effect of dopamine in Drosophila. The short sleep phenotype of the DAT mutant was completely rescued by an additional mutation in the DA1 (also known as DopR) gene, but expression of wild-type DA1 in the dFSB restored the short sleep phenotype. We found anatomical and physiological connections between dopamine neurons and the dFSB neuron. Finally, we used mosaic analysis with a repressive marker and found that a single dopamine neuron projecting to the FSB activated arousal. These results suggest that a local dopamine pathway regulates sleep.

Butcher N.J.,Dalhousie University | Friedrich A.B.,Max Planck Institute For Neurobiologie | Lu Z.,Dalhousie University | Tanimoto H.,Max Planck Institute For Neurobiologie | Meinertzhagen I.A.,Dalhousie University
Journal of Comparative Neurology | Year: 2012

To investigate how sensory information is processed, transformed, and stored within an olfactory system, we examined the anatomy of the input region, the calyx, of the mushroom bodies of Drosophila melanogaster. These paired structures are important for various behaviors, including olfactory learning and memory. Cells in the input neuropil, the calyx, are organized into an array of microglomeruli each comprising the large synaptic bouton of a projection neuron (PN) from the antennal lobe surrounded by tiny postsynaptic neurites from intrinsic Kenyon cells. Extrinsic neurons of the mushroom body also contribute to the organization of microglomeruli. We employed a combination of genetic reporters to identify single cells in the Drosophila calyx by light microscopy and compared these with cell shapes, synapses, and circuits derived from serial-section electron microscopy. We identified three morphological types of PN boutons, unilobed, clustered, and elongated; defined three ultrastructural types, with clear- or dense-core vesicles and those with a dark cytoplasm having both; reconstructed diverse dendritic specializations of Kenyon cells; and identified Kenyon cell presynaptic sites upon extrinsic neurons. We also report new features of calyx synaptic organization, in particular extensive serial synapses that link calycal extrinsic neurons into a local network, and the numerical proportions of synaptic contacts between calycal neurons. All PN bouton types had more ribbon than nonribbon synapses, dark boutons particularly so, and ribbon synapses were larger and with more postsynaptic elements (2-14) than nonribbon (1-10). The numbers of elements were in direct proportion to presynaptic membrane area. Extrinsic neurons exclusively had ribbon synapses. © 2012 Wiley Periodicals, Inc.

Looger L.L.,Howard Hughes Medical Institute | Griesbeck O.,Max Planck Institute For Neurobiologie
Current Opinion in Neurobiology | Year: 2012

Recording activity from identified populations of neurons is a central goal of neuroscience. Changes in membrane depolarization, particularly action potentials, are the most important features of neural physiology to extract, although ions, neurotransmitters, neuromodulators, second messengers, and the activation state of specific proteins are also crucial. Modern fluorescence microscopy provides the basis for such activity mapping, through multi-photon imaging and other optical schemes. Probes remain the rate-limiting step for progress in this field: they should be bright and photostable, and ideally come in multiple colors. Only protein-based reagents permit chronic imaging from genetically specified cells. Here we review recent progress in the design, optimization and deployment of genetically encoded indicators for calcium ions (a proxy for action potentials), membrane potential, and neurotransmitters. We highlight seminal experiments, and present an outlook for future progress. © 2011 Elsevier Ltd.

Kuspert M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Hammer A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Bosl M.R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Wegner M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Wegner M.,Max Planck Institute For Neurobiologie
Nucleic Acids Research | Year: 2011

The HMG-domain transcription factor Sox10 is expressed throughout oligodendrocyte development and is an important component of the transcriptional regulatory network in these myelin-forming CNS glia. Of the known Sox10 regulatory regions, only the evolutionary conserved U2 enhancer in the distal 5′-flank of the Sox10 gene exhibits oligodendroglial activity. We found that U2 was active in oligodendrocyte precursors, but not in mature oligodendrocytes. U2 activity also did not mediate the initial Sox10 induction after specification arguing that Sox10 expression during oligodendroglial development depends on the activity of multiple regulatory regions. The oligodendroglial bHLH transcription factor Olig2, but not the closely related Olig1 efficiently activated the U2 enhancer. Olig2 bound U2 directly at several sites including a highly conserved one in the U2 core. Inactivation of this site abolished the oligodendroglial activity of U2 in vivo. In contrast to Olig2, the homeodomain transcription factor Nkx6.2 repressed U2 activity. Repression may involve recruitment of Nkx6.2 to U2 and inactivation of Olig2 and other activators by protein-protein interactions. Considering the selective expression of Nkx6.2 at the time of specification and in differentiated oligodendrocytes, Nkx6.2 may be involved in limiting U2 activity to the precursor stage during oligodendrocyte development. The Author(s) 2010. Published by Oxford University Press.2010This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. © The Author(s) 2010.

Schifferer M.,Max Planck Institute For Neurobiologie | Griesbeck O.,Max Planck Institute For Neurobiologie
Journal of the American Chemical Society | Year: 2012

Here, we describe a reporter system that consists of a FRET biosensor and its corresponding aptamer. The FRET biosensor employs the synthetic aptamer binding peptide Rsg1.2 sandwiched between mutants of the Green Fluorescent Protein and undergoes FRET when binding its corresponding Rev Responsive Element (RRE) RNA aptamer. We developed a novel approach to engineer FRET biosensors by linker extension and screening to improve signal strength of the biosensor which we called VAmPIRe (Viral Aptamer binding Peptide based Indicator for RNA detection). We demonstrate that the system is quantitative, reversible and works with high specificity in vitro and in vivo in living bacteria and mammalian cells. Thus, VAmPIRe may become valuable for RNA localizations and as a dynamic RNA-based reporter for live cell imaging. Moreover, functional screening of large libraries as demonstrated here may become applicable to optimize some of the many FRET biosensors of cellular signaling. © 2012 American Chemical Society.

Wahlbuhl M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Reiprich S.,Friedrich - Alexander - University, Erlangen - Nuremberg | Vogl M.R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Bosl M.R.,Max Planck Institute For Neurobiologie | Wegner M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Nucleic Acids Research | Year: 2012

The Sox10 transcription factor is a central regulator of vertebrate neural crest and nervous system development. Its expression is likely controlled by multiple enhancer elements, among them U3 (alternatively known as MCS4). Here we analyze U3 activity to obtain deeper insights into Sox10 function and expression in the neural crest and its derivatives. U3 activity strongly depends on the presence of Sox10 that regulates its own expression as commonly observed for important developmental regulators. Sox10 bound directly as monomer to at least three sites in U3, whereas a fourth site preferred dimers. Deletion of these sites efficiently reduced U3 activity in transfected cells and transgenic mice. In stimulating the U3 enhancer, Sox10 synergized with many other transcription factors present in neural crest and developing peripheral nervous system including Pax3, FoxD3, AP2α, Krox20 and Sox2. In case of FoxD3, synergism involved Sox10-dependent recruitment to the U3 enhancer, while Sox10 and AP2α each had to bind to the regulatory region. Our study points to the importance of autoregulatory activity and synergistic interactions for maintenance of Sox10 expression and functional activity of Sox10 in the neural crest regulatory network. © 2011 The Author(s).

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