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.
Schnaitmann C.,Max Planck Institute For Neurobiologie |
Schnaitmann C.,Albert Ludwigs University of Freiburg |
Garbers C.,Ludwig Maximilians University of Munich |
Wachtler T.,Ludwig Maximilians University of Munich |
And 3 more authors.
Current Biology | Year: 2013
Background Color vision is commonly assumed to rely on photoreceptors tuned to narrow spectral ranges. In the ommatidium of Drosophila, the four types of so-called inner photoreceptors express different narrow-band opsins. In contrast, the outer photoreceptors have a broadband spectral sensitivity and were thought to exclusively mediate achromatic vision. Results Using computational models and behavioral experiments, we demonstrate that the broadband outer photoreceptors contribute to color vision in Drosophila. The model of opponent processing that includes the opsin of the outer photoreceptors scored the best fit to wavelength discrimination data. To experimentally uncover the contribution of individual photoreceptor types, we restored phototransduction of targeted photoreceptor combinations in a blind mutant. Dichromatic flies with only broadband photoreceptors and one additional receptor type can discriminate different colors, indicating the existence of a specific output comparison of the outer and inner photoreceptors. Furthermore, blocking interneurons postsynaptic to the outer photoreceptors specifically impaired color but not intensity discrimination. Conclusions Our findings show that receptors with a complex and broad spectral sensitivity can contribute to color vision and reveal that chromatic and achromatic circuits in the fly share common photoreceptors. © 2013 Elsevier Ltd.
Placais P.-Y.,Paris West University Nanterre La Défense |
Trannoy S.,Paris West University Nanterre La Défense |
Trannoy S.,Harvard University |
Friedrich A.B.,Max Planck Institute For Neurobiologie |
And 3 more authors.
Cell Reports | Year: 2013
One of the challenges facing memory research is to combine network- and cellular-level descriptions of memory encoding. In this context, Drosophila offers the opportunity to decipher, down to single-cell resolution, memory-relevant circuits in connection with the mushroom bodies (MBs), prominent structures for olfactory learning and memory. Although the MB-afferent circuits involved in appetitive learning were recently described, the circuits underlying appetitive memory retrieval remain unknown. We identified two pairs of cholinergic neurons efferent from the MB α vertical lobes, named MB-V3, that are necessary for the retrieval of appetitive long-term memory (LTM). Furthermore, LTM retrieval was correlated to an enhanced response to the rewarded odor in these neurons. Strikingly, though, silencing the MB-V3 neurons did not affect short-term memory (STM) retrieval. This finding supports a scheme of parallel appetitive STM and LTM processing
Yamagata N.,Tohoku University |
Yamagata N.,Max Planck Institute For Neurobiologie |
Ichinose T.,Tohoku University |
Ichinose T.,Max Planck Institute For Neurobiologie |
And 8 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015
Drosophila melanogaster can acquire a stable appetitive olfactory memory when the presentation of a sugar reward and an odor are paired. However, the neuronal mechanisms by which a single training induces long-term memory are poorly understood. Here we show that two distinct subsets of dopamine neurons in the fly brain signal reward for short-term (STM) and long-term memories (LTM). One subset induces memory that decays within several hours, whereas the other induces memory that gradually develops after training. They convey reward signals to spatially segregated synaptic domains of the mushroom body (MB), a potential site for convergence. Furthermore, we identified a single type of dopamine neuron that conveys the reward signal to restricted subdomains of the mushroom body lobes and induces long-term memory. Constant appetitive memory retention after a single training session thus comprises two memory components triggered by distinct dopamine neurons.
Finzsch M.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Schreiner S.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Kichko T.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Reeh P.,Friedrich - Alexander - University, Erlangen - Nuremberg |
And 4 more authors.
Journal of Cell Biology | Year: 2010
Mutations in the transcription factor SOX10 cause neurocristopathies, including Waardenburg-Hirschsprung syndrome and peripheral neuropathies in humans. This is partly attributed to a requirement for Sox10 in early neural crest for survival, maintenance of pluripotency, and specification to several cell lineages, including peripheral glia. As a consequence, peripheral glia are absent in Sox10-deficient mice. Intriguingly, Sox10 continues to be expressed in these cells after specification. To analyze glial functions after specification, we specifically deleted Sox10 in immature Schwann cells by conditional mutagenesis. Mutant mice died from peripheral neuropathy before the seventh postnatal week. Nerve alterations included a thinned perineurial sheath, increased lipid and collagen deposition, and a dramatically altered cellular composition. Nerve conduction was also grossly aberrant, and neither myelinating nor non-myelinating Schwann cells formed. Instead, axons of different sizes remained unsorted in large bundles. Schwann cells failed to develop beyond the immature stage and were unable to maintain identity. Thus, our study identifies a novel cause for peripheral neuropathies in patients with SOX10 mutations. © 2010 Finzsch et al.
Aso Y.,Max Planck Institute For Neurobiologie |
Siwanowicz I.,Max Planck Institute For Neurobiologie |
Bracker L.,Max Planck Institute For Neurobiologie |
Ito K.,University of Tokyo |
And 2 more authors.
Current Biology | Year: 2010
A paired presentation of an odor and electric shock induces aversive odor memory in Drosophila melanogaster [1, 2]. Electric shock reinforcement is mediated by dopaminergic neurons [3-5], and it converges with the odor signal in the mushroom body (MB) [2, 6-8]. Dopamine is synthesized in ∼280 neurons that form distinct cell clusters [9-11] and is involved in a variety of brain functions [9, 12-20]. Recently, one of the dopaminergic clusters (PPL1) that includes MB-projecting neurons was shown to signal reinforcement for aversive odor memory . As each dopaminergic cluster contains multiple types of neurons with different projections and physiological characteristics [11, 20], functional understanding of the circuit for aversive memory requires cellular identification. Here, we show that MB-M3, a specific type of dopaminergic neurons in the PAM cluster, is preferentially required for the formation of labile memory. Strikingly, flies formed significant aversive odor memory without electric shock when MB-M3 was selectively stimulated together with odor presentation. In addition, we identified another type of dopaminergic neurons in the PPL1 cluster, MB-MP1, which can induce aversive odor memory. As MB-M3 and MB-MP1 target the distinct subdomains of the MB, these reinforcement circuits might induce different forms of aversive memory in spatially segregated synapses in the MB. © 2010 Elsevier Ltd.
Aso Y.,Max Planck Institute For Neurobiologie |
Aso Y.,Howard Hughes Medical Institute |
Herb A.,University of Würzburg |
Ogueta M.,University of Würzburg |
And 9 more authors.
PLoS Genetics | Year: 2012
Animals acquire predictive values of sensory stimuli through reinforcement. In the brain of Drosophila melanogaster, activation of two types of dopamine neurons in the PAM and PPL1 clusters has been shown to induce aversive odor memory. Here, we identified the third cell type and characterized aversive memories induced by these dopamine neurons. These three dopamine pathways all project to the mushroom body but terminate in the spatially segregated subdomains. To understand the functional difference of these dopamine pathways in electric shock reinforcement, we blocked each one of them during memory acquisition. We found that all three pathways partially contribute to electric shock memory. Notably, the memories mediated by these neurons differed in temporal stability. Furthermore, combinatorial activation of two of these pathways revealed significant interaction of individual memory components rather than their simple summation. These results cast light on a cellular mechanism by which a noxious event induces different dopamine signals to a single brain structure to synthesize an aversive memory. © 2012 Aso et al.
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 (http://creativecommons.org/ 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).