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The airy scan detector for improved sensitivity and resolution analysis of functional neuroanatomy, neuronal regulation, and pericyte biology

English title The airy scan detector for improved sensitivity and resolution analysis of functional neuroanatomy, neuronal regulation, and pericyte biology
Applicant Fritschy Jean-Marc
Number 170804
Funding scheme R'EQUIP
Research institution Institut für Pharmakologie und Toxikologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2017 - 31.03.2018
Approved amount 192'000.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Cellular Biology, Cytology

Keywords (8)

Stem cells; Neurovascular unit; eGFP; Fluorescence imaging; Immunohistochemistry; Synaptic transmission; Synaptic plasticity; GABAA receptors

Lay Summary (German)

Lead
Der Airyscan Detektor ist eine neue Technologie der Konfokaler-Mikroskopie, die eine deutliche Verbesserung der Auflösung und der Empfindlichkeit (Signal - to - Noise Ratio) einherbringtEin solches Gerät wird hier beantragt, um die Forschungsprojekte mehrerer Gruppen am Institut für Pharmakologie und Toxikologie der Universität Zürich voranzubringen.
Lay summary
Hochauflösende mikroskopische Bildgebung mit subzellulärer Auflösung ist eine essentielle Technologie für Untersuchungen der Hirnstruktur, unter anderem der synaptischen Verschaltungen zwischen Nervenzellen. Solche Untersuchungen werden am effektivsten mittels konfokaler Mikroskopie durchgeführt. Die Forschungsgruppen des Instituts für Pharmakologie und Toxikologie sind seit Jahren auf konfokale Mikroskopie angesetzt und die Mehrzahl der Publikationen des Instituts beinhalten Ergebnisse mit dieser Methode. Trotz erfolgreicher Anwendung dieser Technologie gibt es zahlreiche Projekte am Institut, die von einer besseren Auflösung und/oder einer höheren Empfindlichkeit der Detektion von schwachen Signalen profitieren würden. Die Firma Carl Zeiss AG hat vor einem Jahr eine neue Detektionstechnologie, den Airyscan Detektor, auf dem Markt eingeführt. Dieses einzigartige Gerät beruht auf einem Array von 32 Detektoren, die das gesamte emittierte Licht aufnehmen und es ermöglichen, die genaue Quelle des Signals zurückzurechnen, was die Auflösung und die Empfindlichkeit des Mikroskops wesentlich erhöht. Dieser technischer Vorsprung wird in einem herkömmlichen (aber state-of-the-art) Konfokalmikroskop integriert, so dass routine Anwendungen neben dieser spitzen Anwendung möglich sind, was in einer Multiuser Umgebung von grossen Vorteil ist. In diesem R'Equip-Antrag ersuchen wir die Teilfinanzierung eines LSM800 mit Airyscan detector, um die Forschungsprojekte am Institut für Pharmakologie und Toxikologie weiter voranbringen zu können.
Direct link to Lay Summary Last update: 25.03.2017

Responsible applicant and co-applicants

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
GLIA Meeting Poster The Impact of Astrocytic Gap Junction Coupling on Neuronal Function and Energy Metabolism 08.07.2018 Edinburgh, Great Britain and Northern Ireland Weber Bruno;
11th FENS Forum of Neuroscience Poster The GABAergic organization of the striatum 07.07.2018 Berlin, Germany Fritschy Jean-Marc;
Society for Neuroscience Meeting 2018 Poster Dopamine depletion induces circuit-specific alterations of GABAergic transmission in the striatum 03.07.2018 San Diego, CA, United States of America Fritschy Jean-Marc;
International Conference on Brain Energy Metabolism Poster Studying The Impact of Astrocytic Glucose Metabolism On Brain Function In Vivo 07.03.2018 Valvidia, Chile Weber Bruno;
Gordon Research Conference: Inhibition in the CNS 2017 Poster A subset of spinal Pvalb+ interneurons prevent chronic itch like behavior 25.06.2017 Les Diablerets, Switzerland Zeilhofer Hanns Ulrich;


Associated projects

Number Title Start Funding scheme
159867 Post-transcriptional and post-translational cellular signals organize gephyrin scaffolds to facilitate GABAergic synapse plasticity. 01.04.2015 Project funding
166130 GABAA receptor heterogeneity in striatal neurons: significance for Parkinson's disease 01.06.2016 Project funding
156393 Dorsal Horn Neuronal Circuits Processing Itch 01.12.2014 Project funding
176398 Dorsal Horn Neuronal Circuits Processing Itch 01.12.2017 Project funding
156965 Brain pericytes - structure, signaling and hemodynamics 01.11.2014 Project funding
156943 Mechanisms and functional relevance of mitochondrial metabolism for adult neural stem cell activity 01.01.2015 Project funding
147111 Molecules and genes controlling diurnal behavior and physiology 01.04.2013 Project funding

Abstract

This application is a resubmission of a revised proposal submitted in 2015 to the R’Equip program of the Swiss National Science Foundation towards the purchase of a novel confocal microscope equipped with a new detection technology, the Airyscan detector. The reviewers praised the research plan but raised critical comments about the application, questioning in particular the necessity for such an instrument to pursue the proposed research projects. Here, we have addressed all reviewers concerns and provide preliminary evidence for the relevance of this microscope for our research and the ground-breaking nature of the improved features of the requested instrument.The Airyscan detector is a novel device patented by Zeiss to selectively visualize signal emitted from the focal plane in confocal laser scanning microscopy (CLSM). It consists of an array of photodetectors collecting a large fraction of emitted light and generating an image of the focal plane by deconvolution. It replaces the pinhole, a small opening in the light path selectively filtering out all photons emitted from outside the focal plane. The Airyscan technology improves detection sensitivity (signal-to-noise ratio) 1.7 fold and resolution by about 30% in all Cartesian planes. For analyzing submicrometric cellular structures, such as synapses or cytoskeletal organelles, for example, this enhancement represents a huge improvement, enabling analyses that would be out-of-reach without it. The Airycan detector is installed on the last generation of CLSMs and provides a highly needed bridge between routine CLSM imaging and supra-resolution microscopy for multidimensional visualization of fluorescence signals in either fixed biological specimen or living cells and tissues. At the Institute of Pharmacology and Toxicology of the University of Zurich, CLSM represents a major technology supporting research in all units of the Institute since nearly 25 years. In this grant application, we seek financial support to purchase a fully motorized CSLM equipped with an Airyscan detector, along with two conventional, high-sensitivity photodetectors, in order to open new horizons in our research and enable to effectively address questions that have been out of reach so far. The applicant (Prof. Jean-Marc Fritschy) and five co-applicants (Prof. Brown, Prof. Weber, Prof. Zeilhofer, Dr. Tyagarajan; Institute of Pharmacology and Toxicology; Prof. Jessberger, Brain Research Institute) present projects that are readily feasible and open new horizons in the context of on-going research supported by the Swiss National Science Foundation and the ERC. The projects include (1) the elucidation of GABAA receptor heterogeneity in rodent striatum in relation to non-canonical GABA release sites from dopaminergic axons, and their alterations in response to loss of dopaminergic innervation in a model of Parkinson’s disease; (2) identification of interneurons activating presynaptic GABAA receptors in primary afferents of the spinal cord in relation to pain and itch; (3-4) localization, transport, and regulation of dendritically transported mRNA granules in neurons; (5) functional properties of the neurovascular unit and role of pericytes in controlling blood flow through brain capillaries; (6) regulation of cytoplasmic diffusion barriers allowing asymmetric protein sorting between mother and daughter cells during mitosis of neuronal stem cells. The innovative potential of the Airyscan detector extends far beyond these projects, and should contribute to numerous other applications requiring sensitive and high resolution fluorescence imaging. The device would be available in principle for all members of the involved institutes and users of the Center for Microscopy and Image Analysis (ZMB) of the University of Zurich, in agreement with the direction of the ZMB. It is of note, however, that the ZMB is distributed over multiple locations (Irchel campus, University Hospital Zurich, Schlieren campus) and needs several instruments with overlapping capabilities in order to cover the requirements of a vast community of scientists of the University of Zurich. The ZMB is also applying for support of the acquisition of a microscope system with improved detection sensitivity, to be located at the University Hospital Zurich (Dr. H. Hilbi). There is no overlap between the two applications.
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