9 results on '"Josephine Jüttner"'
Search Results
2. High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics
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SangYong Jung, Antoine Huet, Christian Wrobel, Tobias Moser, Kai Bodensiek, Vladan Rankovic, Johannes Schlotte, Thomas Mager, Ernst Bamberg, Lorcan Browne, Katrin Feldbauer, Anna D´Errico, David Lopez de la Morena, Johannes J. Letzkus, Phillip G. Wood, Verena Senn, and Josephine Jüttner
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0301 basic medicine ,Auditory Pathways ,Patch-Clamp Techniques ,Science ,Action Potentials ,General Physics and Astronomy ,Channelrhodopsin ,Stimulus (physiology) ,Biology ,Optogenetics ,Permeability ,General Biochemistry, Genetics and Molecular Biology ,Rats, Sprague-Dawley ,Mice ,Xenopus laevis ,03 medical and health sciences ,Hearing ,Cell Line, Tumor ,medicine ,Animals ,Humans ,lcsh:Science ,Cells, Cultured ,Cochlea ,Neurons ,Multidisciplinary ,Nerve activity ,fungi ,General Chemistry ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Cerebral cortex ,Mutation ,Calcium ,lcsh:Q ,Neuroscience research ,Neuroscience ,Ultrashort pulse ,Signal Transduction - Abstract
Optogenetics revolutionizes basic research in neuroscience and cell biology and bears potential for medical applications. We develop mutants leading to a unifying concept for the construction of various channelrhodopsins with fast closing kinetics. Due to different absorption maxima these channelrhodopsins allow fast neural photoactivation over the whole range of the visible spectrum. We focus our functional analysis on the fast-switching, red light-activated Chrimson variants, because red light has lower light scattering and marginal phototoxicity in tissues. We show paradigmatically for neurons of the cerebral cortex and the auditory nerve that the fast Chrimson mutants enable neural stimulation with firing frequencies of several hundred Hz. They drive spiking at high rates and temporal fidelity with low thresholds for stimulus intensity and duration. Optical cochlear implants restore auditory nerve activity in deaf mice. This demonstrates that the mutants facilitate neuroscience research and future medical applications such as hearing restoration.
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- 2018
3. Cis-regulatory landscapes of four cell types of the retina
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Dominik, Hartl, Arnaud R, Krebs, Josephine, Jüttner, Botond, Roska, and Dirk, Schübeler
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Mice, Transgenic ,Data Resources and Analyses ,DNA Methylation ,Regulatory Sequences, Nucleic Acid ,Retina ,Mice, Inbred C57BL ,Mice ,Retinal Rod Photoreceptor Cells ,Retinal Cone Photoreceptor Cells ,Animals ,Female ,sense organs ,Regulatory Elements, Transcriptional ,Transcriptome - Abstract
The retina is composed of ∼50 cell-types with specific functions for the process of vision. Identification of the cis-regulatory elements active in retinal cell-types is key to elucidate the networks controlling this diversity. Here, we combined transcriptome and epigenome profiling to map the regulatory landscape of four cell-types isolated from mouse retinas including rod and cone photoreceptors as well as rare inter-neuron populations such as horizontal and starburst amacrine cells. Integration of this information reveals sequence determinants and candidate transcription factors for controlling cellular specialization. Additionally, we refined parallel reporter assays to enable studying the transcriptional activity of large collection of sequences in individual cell-types isolated from a tissue. We provide proof of concept for this approach and its scalability by characterizing the transcriptional capacity of several hundred putative regulatory sequences within individual retinal cell-types. This generates a catalogue of cis-regulatory regions active in retinal cell types and we further demonstrate their utility as potential resource for cellular tagging and manipulation.
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- 2017
4. Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno‐associated virus capsid and promoter
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Josephine Jüttner, Luk H. Vandenberghe, Botond Roska, Andreas Reimann, Jean Bennett, Pamela Lagali, Ágota Kacsó, Therese Cronin, Hubertus Kohler, Rachel M. Huckfeldt, Volker Busskamp, Péter Hantz, Scheie Eye Institute [Philadelphia, PA, USA], University of Pennsylvania, Friedrich Miescher Institute for Biomedical Research (FMI), Novartis Research Foundation, Massachusetts Eye and Ear Infirmary [Boston, MA, USA] (Harvard Medical School), Harvard Medical School [Boston] (HMS), Babes-Bolyai University [Cluj-Napoca] (UBB), Department of Genetics [Boston], Ottawa Hospital Research Institute [Ottawa] (OHRI), Cronin, Therese, and University of Pennsylvania [Philadelphia]
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Retinal Bipolar Cells ,promoter optimization Subject Categories Genetics ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,viruses ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Transgene ,Genetic Vectors ,adeno-associated virus ,multi-electrode array ,Gene Therapy & Genetic Disease ,Optogenetics ,Biology ,medicine.disease_cause ,Mice ,Transduction (genetics) ,chemistry.chemical_compound ,Transduction, Genetic ,Gene expression ,medicine ,Animals ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Promoter Regions, Genetic ,optogenetics ,Adeno-associated virus ,Research Articles ,[SDV.IB] Life Sciences [q-bio]/Bioengineering ,HEK 293 cells ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Retinal ,Dependovirus ,Molecular biology ,Cell biology ,Mice, Inbred C57BL ,HEK293 Cells ,[SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging ,Capsid ,chemistry ,Mutagenesis, Site-Directed ,Molecular Medicine ,capsid library ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,sense organs ,promoter optimization ,Neuroscience - Abstract
International audience; In this report, we describe the development of a modified adeno-associated virus (AAV) capsid and promoter for transduction of retinal ON-bipolar cells. The bipolar cells, which are post-synaptic to the photoreceptors, are important retinal targets for both basic and preclinical research. In particular, a therapeutic strategy under investigation for advanced forms of blindness involves using optogenetic molecules to render ON-bipolar cells light-sensitive. Currently, delivery of adequate levels of gene expression is a limiting step for this approach. The synthetic AAV capsid and promoter described here achieves high level of optogenetic transgene expression in ON-bipolar cells. This evokes high-frequency (~100 Hz) spiking responses in ganglion cells of previously blind, rd1, mice. Our vector is a promising vehicle for further development toward potential clinical use.
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- 2014
5. Rods in daylight act as relay cells for cone-driven horizontal cell-mediated surround inhibition
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Antonia Drinnenberg, Gautam B. Awatramani, José-Alain Sahel, Zoltan Raics, Josephine Jüttner, Stuart Trenholm, Rava Azeredo da Silveira, Karl Farrow, Tamas Szikra, Botond Roska, Martin Biel, and Damon A. Clark
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Retina ,genetic structures ,business.industry ,General Neuroscience ,Anatomy ,Biology ,Cell mediated immunity ,Rod ,law.invention ,Optics ,medicine.anatomical_structure ,Relay ,law ,Surround inhibition ,medicine ,Daylight ,sense organs ,business ,Neuroscience ,Bright light - Abstract
Vertebrate vision relies on two types of photoreceptors rods and cones which signal increments in light intensity with graded hyperpolarizations. Rods operate in the lower range of light intensities while cones operate at brighter intensities. The receptive fields of both photoreceptors exhibit antagonistic center surround organization. Here we show that at bright light levels mouse rods act as relay cells for cone driven horizontal cell mediated surround inhibition. In response to large bright stimuli that activate their surrounds rods depolarize. Rod depolarization increases with stimulus size and its action spectrum matches that of cones. Rod responses at high light levels are abolished in mice with nonfunctional cones and when horizontal cells are reversibly inactivated. Rod depolarization is conveyed to the inner retina via postsynaptic circuit elements namely the rod bipolar cells. Our results show that the retinal circuitry repurposes rods when they are not directly sensing light to relay cone driven surround inhibition.
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- 2014
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6. Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity
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Jan Müller, János Németh, Antonia Drinnenberg, Federico Esposti, Arnold Szabo, Zoltán Zsolt Nagy, Josephine Jüttner, Stuart Trenholm, Francis L. Munier, Francisco Cordoba, Botond Roska, Felix Franke, Andreas Hierlemann, Keisuke Yonehara, Michele Fiscella, Akos Kusnyerik, Brigitte Gross Scherf, Jacek Krol, Yonehara, K, Fiscella, M, Drinnenberg, A, Esposti, Federico, Trenholm, S, Krol, J, Franke, F, Gross Scherf, B, Kusnyerik, A, Müller, J, Szabo, A, Jüttnern, J, Cordoba, F, Police Reddy, A, Németh, J, Zsolt Nagy, Z, Munier, F, Hierlemann, A, and Roska, B.
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Retinal Ganglion Cells ,0301 basic medicine ,Interneuron ,Neuroscience(all) ,Motion Perception ,Action Potentials ,Neural Inhibition ,Mice, Transgenic ,Nystagmus ,Biology ,Visual system ,Inhibitory postsynaptic potential ,Retinal ganglion ,Article ,Retina ,03 medical and health sciences ,medicine ,Animals ,Visual Pathways ,General Neuroscience ,Optokinetic reflex ,Cytoskeletal Proteins ,Amacrine Cells ,030104 developmental biology ,medicine.anatomical_structure ,Synapses ,sense organs ,Nerve Net ,medicine.symptom ,Nystagmus, Congenital ,Neuroscience ,Photic Stimulation - Abstract
Summary Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease. Video Abstract, Highlights • FRMD7 is required for the horizontal optokinetic reflex in mice as in humans • Horizontal direction selectivity is lost in the retina of FRMD7 mutant mice • Asymmetry of inhibitory inputs to horizontal DS cells is lost in FRMD7 mutant mice • FRMD7 is expressed in ChAT-expressing cells in the retina of mice and primates, Yonehara et al. show that FRMD7, a gene that is defective in human congenital nystagmus, is required in the mouse retina to establish spatially asymmetric inhibitory inputs from starburst cells to horizontal direction-selective ganglion cells.
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- 2016
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7. How Diverse Retinal Functions Arise from Feedback at the First Visual Synapse
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Antonia Drinnenberg, Rava Azeredo da Silveira, Josephine Jüttner, Felix Franke, Andreas Hierlemann, Péter Hantz, Rei K. Morikawa, Daniel Hillier, Botond Roska, Friedrich Miescher Institute for Biomedical Research (FMI), Novartis Research Foundation, Department of Biosystems Science and Engineering [ETH Zürich] (D-BSSE), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Laboratoire de Physique Statistique de l'ENS (LPS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Princeton Neuroscience Institute [Princeton]
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Retinal Ganglion Cells ,0301 basic medicine ,Retinal Bipolar Cells ,Cell type ,Interneuron ,[SDV]Life Sciences [q-bio] ,Models, Neurological ,Retinal Horizontal Cells ,Biology ,Feedback ,Synapse ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Interneurons ,medicine ,Animals ,Vision, Ocular ,Retina ,General Neuroscience ,Retinal ,Ganglion ,Brain region ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Mouse Retina ,Synapses ,Calcium ,Neuroscience ,Photoreceptor Cells, Vertebrate - Abstract
International audience; Many brain regions contain local interneurons of distinct types. How does an interneuron type contribute to the input-output transformations of a given brain region? We addressed this question in the mouse retina by chemogenetically perturbing horizontal cells, an interneuron type providing feedback at the first visual synapse, while monitoring the light-driven spiking activity in thousands of ganglion cells, the retinal output neurons. We uncovered six reversible perturbation-induced effects in the response dynamics and response range of ganglion cells. The effects were enhancing or suppressive, occurred in different response epochs, and depended on the ganglion cell type. A computational model of the retinal circuitry reproduced all perturbation-induced effects and led us to assign specific functions to horizontal cells with respect to different ganglion cell types. Our combined experimental and theoretical work reveals how a single interneuron type can differentially shape the dynamical properties of distinct output channels of a brain region.
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- 2018
8. The First Stage of Cardinal Direction Selectivity Is Localized to the Dendrites of Retinal Ganglion Cells
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Daniel Hillier, Alexander Ghanem, Botond Roska, Kamill Balint, Karl Farrow, Karl-Klaus Conzelmann, Keisuke Yonehara, Masaharu Noda, Josephine Jüttner, Rachael L. Neve, and Miguel Teixeira
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Retinal Ganglion Cells ,Retinal Bipolar Cells ,Follistatin-Related Proteins ,Patch-Clamp Techniques ,Nerve net ,Neuroscience(all) ,Green Fluorescent Proteins ,Motion Perception ,Action Potentials ,Glutamic Acid ,Mice, Transgenic ,Optogenetics ,Biology ,Visual system ,In Vitro Techniques ,Retinal ganglion ,Retina ,Choline O-Acetyltransferase ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Imaging, Three-Dimensional ,Transduction, Genetic ,Orientation ,medicine ,Animals ,Visual Pathways ,Motion perception ,Axon ,030304 developmental biology ,0303 health sciences ,Microscopy, Confocal ,General Neuroscience ,Anatomy ,Dendrites ,Electric Stimulation ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Animals, Newborn ,Rabies virus ,Synapses ,Nerve Net ,Neuroscience ,030217 neurology & neurosurgery ,Cardinal direction - Abstract
Inferring the direction of image motion is a fundamental component of visual computation and essential for visually guided behavior. In the retina, the direction of image motion is computed in four cardinal directions, but it is not known at which circuit location along the flow of visual information the cardinal direction selectivity first appears. We recorded the concerted activity of the neuronal circuit elements of single direction-selective (DS) retinal ganglion cells at subcellular resolution by combining GCaMP3-functionalized transsynaptic viral tracing and two-photon imaging. While the visually evoked activity of the dendritic segments of the DS cells were direction selective, direction-selective activity was absent in the axon terminals of bipolar cells. Furthermore, the glutamate input to DS cells, recorded using a genetically encoded glutamate sensor, also lacked direction selectivity. Therefore, the first stage in which extraction of a cardinal motion direction occurs is the dendrites of DS cells.
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9. miRNAs 182 and 183 Are Necessary to Maintain Adult Cone Photoreceptor Outer Segments and Visual Function
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Volker Busskamp, Witold Filipowicz, Dasha Nelidova, Josephine Jüttner, Brigitte Gross Scherf, Naoyuki Tanimoto, Ben Tsuda, Michael B. Stadler, Karl Farrow, Tamas Szikra, Mathias W. Seeliger, Claudia Patricia Patino Alvarez, Markus Stoffel, Vithiyanjali Sothilingam, Jacek Krol, Christel Genoud, Janine M Daum, and Botond Roska
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Aging ,Light ,genetic structures ,Color vision ,Neuroscience(all) ,Mice, Transgenic ,Biology ,Retina ,03 medical and health sciences ,Genetic signature ,chemistry.chemical_compound ,Gene Knockout Techniques ,Mice ,0302 clinical medicine ,Retinal Rod Photoreceptor Cells ,microRNA ,medicine ,Animals ,Humans ,Vision, Ocular ,030304 developmental biology ,0303 health sciences ,Blindness ,General Neuroscience ,Cilium ,Retinal ,Anatomy ,medicine.disease ,Cell biology ,MicroRNAs ,chemistry ,Visual function ,Retinal Cone Photoreceptor Cells ,sense organs ,030217 neurology & neurosurgery - Abstract
SummaryThe outer segments of cones serve as light detectors for daylight color vision, and their dysfunction leads to human blindness conditions. We show that the cone-specific disruption of DGCR8 in adult mice led to the loss of miRNAs and the loss of outer segments, resulting in photoreceptors with significantly reduced light responses. However, the number of cones remained unchanged. The loss of the outer segments occurred gradually over 1 month, and during this time the genetic signature of cones decreased. Reexpression of the sensory-cell-specific miR-182 and miR-183 prevented outer segment loss. These miRNAs were also necessary and sufficient for the formation of inner segments, connecting cilia and short outer segments, as well as light responses in stem-cell-derived retinal cultures. Our results show that miR-182- and miR-183-regulated pathways are necessary for cone outer segment maintenance in vivo and functional outer segment formation in vitro.
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