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Computational functions of inhibitory neuronal circuits

English title Computational functions of inhibitory neuronal circuits
Applicant Friedrich Rainer
Number 152833
Funding scheme Project funding (Div. I-III)
Research institution Friedrich Miescher Institute for Biomedical Research
Institution of higher education Institute Friedrich Miescher - FMI
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2014 - 30.09.2017
Approved amount 783'684.00
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Keywords (8)

Interneuron; Neuronal computation; Olfaction; Zebrafish; Optogenetics; Paleocortex; Memory; Olfactory cortex

Lay Summary (German)

Lead
Höhere Gehirnfunktionen entstehen durch Kommunikation zwischen Nervenzellen (Neuronen), die in komplexen „neuronalen Schaltkreisen“ organisiert sind. Einzelne Neurone sind entweder erregend oder inhibierend und kommunizieren mit anderen Nervenzellen über spezialisierte Kontaktstellen, die Synapsen. Inhibitorische Neurone können in verschiedene Subtypen unterteilt und spezifischen Mikro-Schaltkreisen zugeordnet werden, die wahrscheinlich elementare Schritte der Informationsverarbeitung ausführen. Die Analyse solcher Mikro-Schaltkreise durch funktionelle Manipulation bestimmter inhibitorischer Neurone bietet neue Möglichkeiten zur systematischen Untersuchung der Informationsverarbeitung im Gehirn. Dieser Ansatz wird hier verfolgt, um fundamentale Rechenoperationen im Gehirn zu entschlüsseln, die für höhere Gehirnfunktionen von Bedeutung sind.
Lay summary
Das Projekt untersucht Informationsverarbeitung in einer Region des Vorderhirns im Zebrafish (Dp), die homolog zum olfaktorischen Kortex in Säugern ist. Der Zebrafisch bietet als kleiner, genetisch zugänglicher Modellorganismus entscheidende Vorteile zur Analyse neuronaler Schaltkreisfunktionen. Der olfaktorische Kortex und Dp verarbeiten Geruchsinformation, die sie von Neuronen des Riechkolbens in Form komplexer raum-zeitlicher neuronaler Aktivitätsmuster erhalten. Es wird angenommen, dass der olfaktorische Kortex und Dp Operationen ausführen, die zur Bildung eines assoziativen Gedächtnis führen und somit von fundamentaler Bedeutung für höhere Gehirnfunktionen sind. Um diese Operationen zu charakterisieren und bestimmten Mikro-Schaltkreisen zuzuordnen, werden wir die Aktivität bestimmter inhibitorischer Interneurone manipulieren. Hierzu werden wir neuartige optische und andere Methoden einsetzen, mit deren Hilfe die Aktivität von Neuronen durch Licht oder chemische Substanzen mit hoher räumlicher und zeitlicher Präzision gezielt erhöht oder erniedrigt werden kann. Gleichzeitig werden wir die Aktivität vieler Neurone in Dp und anderen Gehirnregionen mittels moderner optischen Methoden messen, um die Auswirkungen auf die Verarbeitung von Geruchsinformation zu untersuchen. Weiterhin werden wir bestimmte Neurone manipulieren und Verhaltensexperimente durchführen, um die Funktion von Mikro-Schaltkreisen während des Lernens und beim Abruf von Gedächtnisinhalten zu studieren. In Fischen mit genetischen Defekten, die im Menschen zu neurologischen Krankheiten führen, werden wir Störungen assoziativer Gehirnfunktionen und die zugrundeliegenden Mechanismen untersuchen. Wir erwarten, dass dieses Projekt fundamentale Mechanismen der Informationsverarbeitung im Gehirn entschlüsseln wird, die die Grundlage höherer Gehirnfunktionen bilden. Darüberhinaus unternimmt das Projekt erste Schritte zur Untersuchung pathophysiologischer Grundlagen neuronaler Krankheiten.
Direct link to Lay Summary Last update: 29.08.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Whitening of odor representations by the wiring diagram of the olfactory bulb
Wanner Adrian A., Friedrich Rainer W. (2020), Whitening of odor representations by the wiring diagram of the olfactory bulb, in Nature Neuroscience, 23(3), 433-442.
A virtual reality system to analyze neural activity and behavior in adult zebrafish
Huang Kuo-Hua, Rupprecht Peter, Frank Thomas, Kawakami Koichi, Bouwmeester Tewis, Friedrich Rainer W. (2020), A virtual reality system to analyze neural activity and behavior in adult zebrafish, in Nature Methods, 17(3), 343-351.
Associative conditioning remaps odor representations and modifies inhibition in a higher olfactory brain area
Frank Thomas, Mönig Nila R., Satou Chie, Higashijima Shin-ichi, Friedrich Rainer W. (2019), Associative conditioning remaps odor representations and modifies inhibition in a higher olfactory brain area, in Nature Neuroscience, 22(11), 1844-1856.
Rapid olfactory discrimination learning in adult zebrafish
Namekawa Iori, Moenig Nila R., Friedrich Rainer W. (2018), Rapid olfactory discrimination learning in adult zebrafish, in Experimental Brain Research, 236(11), 2959-2969.
Precise Synaptic Balance in the Zebrafish Homolog of Olfactory Cortex
Rupprecht Peter, Friedrich Rainer W. (2018), Precise Synaptic Balance in the Zebrafish Homolog of Olfactory Cortex, in Neuron, 100(3), 669-683.e5.
Experience-dependent plasticity of odor representations in the telencephalon of zebrafish
Jacobson Gilad, Rupprecht Peter, Friedrich Rainer W. (2018), Experience-dependent plasticity of odor representations in the telencephalon of zebrafish, in Current Biology, 28, 1-14.
3-dimensional electron microscopic imaging of the zebrafish olfactory bulb and dense reconstruction of neurons
Wanner Adrian A., Genoud Christel, Friedrich Rainer W. (2016), 3-dimensional electron microscopic imaging of the zebrafish olfactory bulb and dense reconstruction of neurons, in Scientific Data, 3, 160100.
Dense EM-based reconstruction of the interglomerular projectome in the zebrafish olfactory bulb
Wanner Adrian A., Genoud Christel, Masudi Tafheem, Siksou L., Friedrich Rainer W. (2016), Dense EM-based reconstruction of the interglomerular projectome in the zebrafish olfactory bulb, in Nature Neuroscience, 19, 816-825.
Remote z-scanning with a macroscopic voice coil motor for fast 3D multiphoton laser scanning microscopy
Rupprecht Peter, Prendergast Andrew, Wyart Claire, Friedrich Rainer W. (2016), Remote z-scanning with a macroscopic voice coil motor for fast 3D multiphoton laser scanning microscopy, in Biomed. Optics Expr., 7(5), 1656-1671.

Datasets

EM image stack of zebrafish olfactory bulb

Author Wanner, Adrian
Persistent Identifier (PID) 10.7281/T1MS3QN7
Repository neurodata.io


Skeleton reconstructions of neurons in zebrafish olfactory bulb

Author Wanner, Adrian
Persistent Identifier (PID) 10.5281/zenodo.58985
Repository zenodo


Outlines of glomeruli in zebrafish olfactory bulb

Author Wanner, Adrian
Persistent Identifier (PID) 10.5281/zenodo.58985
Repository zenodo


Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
International Olfactory Symposium and Workshop Talk given at a conference Learning and inhibition in the zebrafish homolog of olfactory cortex 04.10.2017 Regensburg, Germany Frank Thomas;
FMI Annual meeting Poster Cholinergic modulation of higher olfactory circuits in adult Zebrafish 25.09.2017 Grindelwald, Switzerland Friedrich Rainer; Moressis Anastasios;
FMI Annual Meeting 2017 Poster Towards structure–function analysis of higher olfactory area Dp in adult zebrafish 25.09.2017 Grindelwald, Switzerland Titze Benjamin; Friedrich Rainer;
Neuromodulation of Neural Microcircuits NM2 Conference Talk given at a conference Connectivity and computations in the olfactory bulb 18.09.2017 Lausanne, Switzerland Friedrich Rainer;
Neural Coding, Computation and Dynamics (NCCD) Poster 3. Cooperative Tuning and Timing of Excitatory and Inhibitory Inputs in the Olfactory Cortex Homolog of Zebrafish 17.09.2017 Capbreton, France Rupprecht Peter;
Connectomics symposium Talk given at a conference Deconstruction and reconstruction of olfactory computations 11.09.2017 Fribourg, Switzerland Friedrich Rainer;
Invited Lecture, University of Oslo Individual talk Deconstruction and reconstruction of olfactory computations 19.06.2017 Oslo, Norway Friedrich Rainer;
11th Annual Canadian Neuroscience Meeting Poster Illuminating the function of inhibitory microcircuits in the zebrafish homologue of olfactory cortex 28.05.2017 Montreal, Canada Frank Thomas;
Blankenese Conference Talk given at a conference Deconstruction and reconstruction of olfactory computations 06.05.2017 Hamburg, Germany Friedrich Rainer;
13th Swiss meeting on cellular and molecular neurobiology of mental disease Talk given at a conference Illuminating the function of inhibitory microcircuits in the zebrafish homologue of olfactory cortex 04.05.2017 Giessbach, Switzerland Frank Thomas;
Max Planck/HHMI Connectomics Conference Talk given at a conference SBEMimage: versatile acquisition software for serial block-face electron microscopy 09.04.2017 Berlin, Germany Titze Benjamin;
Max Planck/HHMI Connectomics Conference Talk given at a conference Reconstructing neuronal computations 09.04.2017 Berlin, Germany Friedrich Rainer;
Max Planck/HHMI Connectomics Conference Talk given at a conference Super-Resolution Methods for EM Connectomics 09.04.2017 Berlin, Germany Gerhard Stephan;
Max Planck/HHMI Connectomics Conference Talk given at a conference The synaptic connectome of the zebrafish olfactory bulb 09.04.2017 Berlin, Germany Wanner Adrian;
12th Göttingen Meeting of the German Neuroscience Society Poster Illuminating the function of inhibitory microcircuits in the zebrafish homolog of olfactory cortex 22.03.2017 Göttingen, Germany Friedrich Rainer; Frank Thomas;
12th Göttingen Meeting of the German Neuroscience Society Talk given at a conference Deconstruction and reconstruction of olfactory computations in zebrafish 22.03.2017 Göttingen, Germany Friedrich Rainer;
COSYNE workshop Talk given at a conference Neuronal computations for olfactory pattern classification 23.02.2017 Salt Lake City, United States of America Friedrich Rainer;
19th annual meeting, Swiss Society for Neuroscience Poster Illuminating the function of inhibitory microcircuits in the zebrafish homolog of olfactory cortex 27.01.2017 Basel, Switzerland Friedrich Rainer; Frank Thomas;
19th annual meeting, Swiss Society for Neuroscience Poster Balance and Imbalance of Inputs to Neurons of the Olfactory Cortex Homolog in Zebrafish 27.01.2017 Basel, Switzerland Friedrich Rainer; Rupprecht Peter;
Neural circuits: connectivity and plasticity Talk given at a conference Deconstruction and reconstruction of olfactory computations 12.12.2016 Lausanne, Switzerland Friedrich Rainer;
Imaging structure and function of the zebrafish brain Talk given at a conference Deconstruction and reconstruction of neuronal circuits for olfaction 01.12.2016 Munich, Germany Friedrich Rainer;
Imaging Structure and Function in the Zebrafish Brain Poster Illuminating the function of inhibitory microcircuits in the zebrafish homologue of olfactory cortex 01.12.2016 Munich, Germany Frank Thomas; Friedrich Rainer;
Imaging Structure and Function in the Zebrafish Brain Poster Cholinergic modulation of higher olfactory circuits in adult Zebrafish 01.12.2016 Munich, Germany Friedrich Rainer; Moressis Anastasios;
46th annual meeting, Society for Neuroscience (SfN) Poster Illuminating the function of inhibitory microcircuits in the zebrafish homolog of olfactory cortex 12.11.2016 San Diego, United States of America Friedrich Rainer; Frank Thomas;
EMBO member meeting Talk given at a conference Neuronal connectivity and computation in olfaction 26.10.2016 Heidelberg, Germany Friedrich Rainer;
Annual meeting of the Spanish Society for Developmental Biology Talk given at a conference Deconstruction and reconstruction of neuronal circuits for olfaction 19.10.2016 Girona, Spain Friedrich Rainer;
FMI Annual meeting Poster Optogenetic dissection of neuromodulation in the Zebrafish homolog of olfactory cortex 17.09.2016 Basel, Switzerland Friedrich Rainer; Moressis Anastasios;
Cellular and molecular neurobiology of mental disease Talk given at a conference Deconstruction and reconstruction of neuronal computations 19.05.2016 Giessbach, Switzerland Friedrich Rainer;
HHMI Janelia Conference: High-resolution circuit reconstruction Talk given at a conference Deconstruction and reconstruction of neuronal computations for olfaction 10.04.2016 HHMI Janelia Farm, United States of America Friedrich Rainer;
Invited lecture, UCL Gatsby Center Individual talk Deconstruction and reconstruction of neuronal circuits for olfaction 20.01.2016 London, Great Britain and Northern Ireland Friedrich Rainer;
Invited lecture, University of Oxford Individual talk Deconstruction and reconstruction of neuronal circuits for olfaction 18.01.2016 Oxford, Great Britain and Northern Ireland Friedrich Rainer;
Society for Neuroscience Meeting Poster Variability and adaptation of odor representations in the zebrafish homolog of olfactory cortex 17.10.2015 Chicago, United States of America Jacobson Gilad;
Frontiers in Neurophotonics Symposium Talk given at a conference Deconstruction and reconstruction of neuronal circuits for olfaction 03.10.2015 Quebec City, Canada Friedrich Rainer;
FMI Annual meeting Poster Variability and adaptation of odor representations in the zebrafish homolog of olfactory cortex 16.09.2015 Grindelwald, Switzerland Jacobson Gilad; Friedrich Rainer;
Invited lecture, Ecole Normale Superieure Individual talk Deconstruction and reconstruction of neuronal circuits for olfaction 29.06.2015 Paris, France Friedrich Rainer;
European Zebrafish Meeting Talk given at a conference Deconstructing and reconstructing neuronal circuits for olfaction 28.06.2015 Oslo, Norway Friedrich Rainer;
FMI - Kavli Institute retreat Talk given at a conference Variability and adaptation in higher order odour representations 28.06.2015 Rungstedtsgaard, Denmark Jacobson Gilad;
Gordon Conference “Modulation of neuronal circuits and behavior” Talk given at a conference Deconstructing and reconstructing neuronal circuits for olfaction 21.06.2015 Hongkong, China Friedrich Rainer;
HHMI Janelia workshop Zebrafish systems biology Talk given at a conference Neuronal circuits and computations in olfaction 22.04.2015 HHMI Janelia, United States of America Friedrich Rainer;
Invited lecture, Harvard University Individual talk Neuronal circuits and computations in olfaction 01.04.2015 Boston, United States of America Friedrich Rainer;
"Sunposium" Talk given at a conference Neuronal circuits and computations in olfaction 30.03.2015 Jupiter, FL, United States of America Friedrich Rainer;
Invited lecture, Bernstein Center Individual talk Neuronal circuits and computations in the olfactory bulb 04.02.2015 Berlin, Germany Friedrich Rainer;
Imaging structure and function in the zebrafish brain Talk given at a conference Neuronal circuits and computations in olfaction 14.12.2014 Paris, France Friedrich Rainer;


Self-organised

Title Date Place
Gordon Conference “Modulation of neuronal circuits and behavior” 04.06.2017 Newry, ME, United States of America
Basel Neuroscience meeting: Bench-to-Bedsite 05.02.2016 Basel, Switzerland
Basel Neuroscience meeting: Bench-to-Bedsite 13.02.2015 Basel, Switzerland

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Meeting of veterinary committee for animal experiments Talk 25.03.2015 Basel, Switzerland Friedrich Rainer;
Animal training course (LTK) Talk 28.10.2014 basel, Switzerland Friedrich Rainer;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Woche des Gehirns Basel German-speaking Switzerland 2017

Awards

Title Year
CV Starr fellowship (Princeton fellow including salary) 2017
Ruth Chiquet Originality Award (FMI) 2017
Winner of Spikefinder Challenge (competition organized by HHMI/Uni Tübingen) 2017
Ruth Chiquet Originality Award (FMI) 2016

Associated projects

Number Title Start Funding scheme
172925 Bottom-up and top-down neuronal computations in olfaction 01.04.2018 Project funding (Div. I-III)
135196 Elementary computational functions of inhibitory neuronal circuits 01.10.2011 Project funding (Div. I-III)

Abstract

Background and general aim: The central nervous system of vertebrates contains a diverse spectrum of inhibitory interneurons that are associated with specific microcircuits. The goal of this project is to analyze the computational functions of such microcircuits by studying and manipulating defined interneurons. The project takes advantage of zebrafish as a small genetic vertebrate model and focuses on a higher olfactory brain area (Dp) that is homologous to paleocortex (olfactory cortex). Dp is thought to establish Gestalt representations of olfactory objects and to function as an auto-associative network that stores odor-encoding activity patterns in memory. We will analyze the elementary cortical computations underlying such higher brain functions by genetic targeting of defined interneurons, measurements of neuronal activity patterns, functional manipulations of defined interneurons by opto- and pharmacogenetics, and behavioral experiments. The following specific aims will be addressed:1.Elementary computations in olfactory cortex/Dp. Genetically defined interneurons will be characterized and manipulated in order to define the associated microcircuits, to examine their canonical computational functions, and to explore their role in olfactory processing. 2.Neuromodulation of microcircuits. Using optogenetic approaches we will examine how neuromodulatory inputs, particularly dopaminergic and cholinergic inputs, control the functions of microcircuits. We will specifically test the hypothesis that neuromodulation regulates inhibitory microcircuits to control neuronal plasticity and information storage in autoassociative networks. 3.Behavioral functions of elementary cortical computations. Opto- and pharmacogenetic manipulations of defined interneurons will be combined with behavioral assays to examine how elementary cortical computations influence behavior. We will specifically test the hypothesis that inhibitory microcircuits stabilize odor perception by stabilizing odor-encoding activity patterns.4.Abnormal microcircuit function in genetic disease models. We will explore the possibility to study dysfunctions of microcircuits in zebrafish carrying mutations that have been associated with specific diseases in humans.Expected value: We expect to uncover direct relationships between microcircuit structure, function and dysfunction that provide quantitative insights into elementary cortical computations. The combination of functional manipulations and behavioral experiments is expected to establish direct links between neuronal circuit function and defined behaviors. The general goal is to provide systematic and mechanistic insights into cortical computations underlying higher brain functions.
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