Project

Back to overview

Elementary computational functions of inhibitory neuronal circuits

English title Elementary computational functions of inhibitory neuronal circuits
Applicant Friedrich Rainer
Number 135196
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 01.10.2011 - 30.09.2014
Approved amount 784'135.00
Show all

All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Biophysics

Keywords (7)

Neuronal circuit; Interneuron; Optogenetics; Olfactory bulb; Olfactory cortex; Zebrafish; Neuronal computation

Lay Summary (English)

Lead
Lay summary

The communication between nerve cells (neurons) in a network is essential for information processing in the brain. Neurons do not only communicate by excitatory connections, but many connections are inhibitory and, thus suppress the activity of target neurons. Although such inhibitory connections are essential, their precise roles in information processing are often not well understood. Inhibitory interactions are often local and mediated by a wide variety of different neuron types. Individual types of inhibitory neurons may therefore be involved in specific “microcircuits” that perform different elementary computational functions. This offers the opportunity to systematically dissect the function of complex neuronal circuits by manipulating the function of specific types of interneurons, analyzing the effect on defined microcircuits, and examining the consequences at the behavioral level.

To analyze the functions of inhibitory neurons and microcircuits, we will focus on the olfactory system of zebrafish and perform experiments in an ex-vivo brain preparation. Specifically, we will study the first olfactory processing center, the olfactory bulb, and a higher area in the forebrain that is homologous to olfactory cortex. Because the organization and function of both areas is likely preserved throughout vertebrates, we expect results to be of general relevance. Previous studies have uncovered a variety of fundamental computations that are performed in these brain areas, but the underlying mechanisms are still poorly understood. To address these questions, we will measure and manipulate the activity of interneurons by a variety of approaches: (1) neuronal activity will be measured by electrical recordings or high-resolution optical methods (multiphoton microscopy) in the intact brain. Multiphoton microscopy allows us to measure activity patterns evoked by olfactory stimuli across large numbers of neurons. (2) Different types of interneurons will be labelled genetically by introducing fluorescent proteins. (3) The activity of neurons will be manipulated optically using novel “optogenetic” approaches that allow for the excitation or inhibition of neurons by light with high precision. In addition, we will use “pharmacogenetic” approaches that allow for the inhibition of specific neurons by pharmacological agents. Together, these experiments are expected to elucidate the role of different types of inhibitory neurons in their microcircuits and identify the elementary computations by these microcircuits. Based on this knowledge, we will then test whether manipulating elementary computations has consequences on perception and behavior. Together, these results are expected to provide insights into elementary mechanisms of information processing in the brain. Furthermore, we expect to establish causal links between elementary computations and their behavioral consequences, a key step in understanding brain function. Such knowledge will be valuable to understand neuronal dysfunctions in disease and design strategies for treatments of neurological disorders.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Amygdala interneuron subtypes control fear learning through disinhibition.
Wolff Steffen B E, Gründemann Jan, Tovote Philip, Krabbe Sabine, Jacobson Gilad A, Müller Christian, Herry Cyril, Ehrlich Ingrid, Friedrich Rainer W, Letzkus Johannes J, Lüthi Andreas (2014), Amygdala interneuron subtypes control fear learning through disinhibition., in Nature, 509(7501), 453-8.
Neuronal circuits and computations: pattern decorrelation in the olfactory bulb.
Friedrich Rainer W, Wiechert Martin T (2014), Neuronal circuits and computations: pattern decorrelation in the olfactory bulb., in FEBS letters, 588(15), 2504-13.
Stereotopy versus stochasticity in olfaction.
Friedrich Rainer W, Moressis Anastasios, Frank Thomas (2014), Stereotopy versus stochasticity in olfaction., in Nature neuroscience, 17(2), 147-9.
Analyzing the structure and function of neuronal circuits in zebrafish.
Friedrich Rainer W, Genoud Christel, Wanner Adrian A (2013), Analyzing the structure and function of neuronal circuits in zebrafish., in Frontiers in neural circuits, 7, 71-71.
Equalization of odor representations by a network of electrically coupled inhibitory interneurons.
Zhu Peixin, Frank Thomas, Friedrich Rainer W (2013), Equalization of odor representations by a network of electrically coupled inhibitory interneurons., in Nature neuroscience, 16(11), 1678-86.
Functional development of the olfactory system in zebrafish.
Miyasaka Nobuhiko, Wanner Adrian A, Li Jun, Mack-Bucher Julia, Genoud Christel, Yoshihara Yoshihiro, Friedrich Rainer W (2013), Functional development of the olfactory system in zebrafish., in Mechanisms of development, 130, 336-346.
Neural Circuits: Random Design of a Higher-Order Olfactory Projection
Jacobson Gilad A., Friedrich Rainer W. (2013), Neural Circuits: Random Design of a Higher-Order Olfactory Projection, in CURRENT BIOLOGY, 23(10), 448-451.
Neuronal computations in the olfactory system of zebrafish.
Friedrich Rainer W (2013), Neuronal computations in the olfactory system of zebrafish., in Annual review of neuroscience, 36, 383-402.
Dopaminergic modulation of mitral cells and odor responses in the zebrafish olfactory bulb.
Bundschuh Sebastian T, Zhu Peixin, Schärer Yan-Ping Zhang, Friedrich Rainer W (2012), Dopaminergic modulation of mitral cells and odor responses in the zebrafish olfactory bulb., in Journal of neuroscience, 32(20), 6830-6840.
Dopaminergic modulation of synaptic transmission and neuronal activity patterns in the zebrafish homolog of olfactory cortex
Schärer Yan-Ping, Shum Jennifer, Moressis Anastasios, Friedrich Rainer W. (2012), Dopaminergic modulation of synaptic transmission and neuronal activity patterns in the zebrafish homolog of olfactory cortex, in Front. Neural Circuits, 6, 76.
High-resolution optical control of spatiotemporal neuronal activity patterns in zebrafish using a digital micromirror device
Zhu P., Fajardo O., Shum J., Zhang Schärer Y.-P., Friedrich R. W. (2012), High-resolution optical control of spatiotemporal neuronal activity patterns in zebrafish using a digital micromirror device, in Nature Protocols, 7, 1410-1425.
Neuronal filtering of multiplexed odour representations.
Blumhagen Francisca, Zhu Peixin, Shum Jennifer, Schärer Yan-Ping Zhang, Yaksi Emre, Deisseroth Karl, Friedrich Rainer W (2011), Neuronal filtering of multiplexed odour representations., in Nature, 479(7374), 493-498.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
HHMI Janelia Max Planck Meeting on Connectomics Talk given at a conference Topology and function of neuronal circuits for olfaction 07.09.2014 Berlin, Germany Friedrich Rainer;
FEBS-EMBO meeting Talk given at a conference Reverse engineering of neuronal circuits for olfaction 02.09.2014 Paris, France Friedrich Rainer;
FENS meeting Poster Illuminating the role of inhibitory microcircuits in higher-order olfactory processing in zebrafish 05.07.2014 Milano, Italy Frank Thomas; Friedrich Rainer; Jacobson Gilad;
Neural Networks in the Arctic Poster Illuminating the role of inhibitory microcircuits in higher-order olfactory processing in zebrafish 05.06.2014 Spitzbergen, Norway Frank Thomas; Friedrich Rainer;
FENS meeting satellite symposium Talk given at a conference Functional dissection of neuronal circuits for olfaction in zebrafish: reading and writing neuronal activity by light 04.06.2014 Milano, Italy Friedrich Rainer;
SINTN lectures Individual talk Reverse engineering of neuronal circuits in the olfactory bulb 27.03.2014 Stanford, United States of America Friedrich Rainer;
Max Planck Institute for Brain Research Lecture series Individual talk Reverse engineering of neuronal circuits for olfaction 19.02.2014 Frankfurt, Germany Friedrich Rainer;
Graduate School Symposium Talk given at a conference Analysis of neuronal circuit structure and function in zebrafish 22.01.2014 Fribourg, Switzerland Friedrich Rainer;
Invited Lecture, Haifa University and Technion Individual talk Neuronal circuits for pattern classification in the olfactory system 24.11.2013 Haifa, Israel Friedrich Rainer;
KSOP conference Talk given at a conference Reverse engineering of neuronal circuits using light 05.11.2013 Karlsruhe, Germany Friedrich Rainer;
Assembly and Function of neuronal circuits (Ascona meeting) Talk given at a conference Stability and sensitivity of odor representations in the olfactory bulb 29.09.2013 Ascona, Switzerland Friedrich Rainer;
HFSP meeting Talk given at a conference Mechanistic analysis of neuronal circuit structure and function 07.07.2013 Strasbourg, France Friedrich Rainer;
Cell Press Symposium Genes, Circuits,Behavior Talk given at a conference Neuronal circuits and computations in the zebrafish olfactory system: scents and sensitivity 03.06.2013 Toronto, Canada Friedrich Rainer;
Dynamics of memory Talk given at a conference Pattern classification in the olfactory system 13.05.2013 Janelia Farm HHMI, United States of America Friedrich Rainer;
Dynamics of neuronal systems Talk given at a conference Scents and sensitivity: an olfactory microcircuit that stabilizes neuronal activity patterns 18.03.2013 Freiburg, Germany Friedrich Rainer;
Invited lecture, Janelia Farm Individual talk Scents and sensitivity: an olfactory microcircuit that stabilizes neuronal activity patterns 15.01.2013 Janelia Farm HHMI, United States of America Friedrich Rainer;
Imaging neuronal circuit structure and function in zebrafish Talk given at a conference Scents and sensitivity: an olfactory microcircuit that stabilizes neuronal activity patterns 07.12.2012 London, Great Britain and Northern Ireland Friedrich Rainer; Zhu Peixin;
Invited seminar, CRG Barcelona Individual talk Neuronal circuits and computations in the olfactory system 09.11.2012 Barcelona, Spain, Spain Friedrich Rainer;
Society for Neuroscience Annual Meeting 2012 Poster Equalization of odor representations in the olfactory bulb 13.10.2012 New Orleans, USA, United States of America Zhu Peixin;
Optogenetics and Pharmacogenetics in Neuronal Function and Dysfunction; 7th Brain Research Conference Talk given at a conference Opto- and pharmacogenetic analysis of neuronal crcuit functions 11.10.2012 New Orleans, USA, United States of America Friedrich Rainer;
Cellular Mechanisms of Sensory Processing (Conference) Talk given at a conference Pattern classification in the olfactory system 08.10.2012 Göttingen, Germany, Germany Friedrich Rainer;
Neurobiology conference, Sendai, Japan Talk given at a conference Neuronal circuits and computations in the olfactory system 25.07.2012 Sendai, Japan, Japan Friedrich Rainer;
Dynamics of memory, FENS meeting Satellite Talk given at a conference Transformations of odor representations 12.07.2012 Barcelona, Spain, Spain Friedrich Rainer;
Cold Spring Harbor Symposium Neuronal Circuits Talk given at a conference Transformations of odor representations 28.03.2012 Cold Spring Harbor Labs, USA, United States of America Friedrich Rainer;


Self-organised

Title Date Place
CIFAR workshop BrainLight 14.01.2014 Montreal, Canada
Neurex meeting: Neuronal circuits and dynamics 10.06.2013 Basel, Switzerland
Illuminating vertebrate olfactory processing (SFN Minisymposium) 17.10.2012 New Orleans, USA, United States of America

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Meeting eidgenössische Kommission für Tierversuche Talk 21.03.2013 Basel, Switzerland Friedrich Rainer;
Nestle Nutrition board annual meeting Talk 20.04.2012 Basel, Switzerland Friedrich Rainer;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Woche des Gehirns German-speaking Switzerland 2014
Talks/events/exhibitions Tage der Genforschung German-speaking Switzerland 2013
Talks/events/exhibitions Zebrafish in neuroscience German-speaking Switzerland 2013
Talks/events/exhibitions Perspectives of high power computing in neurosciences German-speaking Switzerland Western Switzerland Italian-speaking Switzerland Rhaeto-Romanic Switzerland 2012
Media relations: radio, television Various interviews Radio German-speaking Switzerland Italian-speaking Switzerland Rhaeto-Romanic Switzerland Western Switzerland 2012

Awards

Title Year
Academia Europaea Member 2014
EMBO Full Member 2014
Jean-Marie Delwart Prize 2012

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)
152833 Computational functions of inhibitory neuronal circuits 01.10.2014 Project funding (Div. I-III)

Abstract

Background and general aim: Although there can be no doubt that inhibition plays pivotal roles in the brain, the mechanisms by which inhibitory interneurons govern computational properties of neuronal circuits are still poorly defined. Because inhibitory interneurons are diverse and usually local, studying and manipulating interneurons provides an opportunity to analyze canonical computations in neuronal microcircuits and their contributions to higher brain functions. The general goal of the proposed project is to identify mechanisms by which inhibitory interneurons define computational properties of neuronal circuits. Using zebrafish as a model, we will focus on the olfactory bulb and telencephalic area Dp, the homolog of olfactory cortex. Basic computations in the olfactory bulb include the control of overall activity (“volume control”), a decorrelation of overlapping activity patterns, and the classification of odors into discrete output states. Dp (olfactory cortex) is thought to create olfactory object representations and to store odor-encoding activity patterns in auto-associative memory networks. To dissect the function of these circuits we will analyze and manipulate the activity of genetically defined interneurons by 2-photon calcium imaging, electrophysiology and optogenetics. Moreover, we will explore the functions of defined microcircuits in learning behaviors. Specific aims:1. Tools: transgenic zebrafish lines. Transgenes that allow for the manipulation of neuronal activity by light and drugs will be expressed in specific neuron types.2. Function of periglomerular cells (PGCs) in the OB. PGCs are a major class of GABAergic interneurons in the OB. We will measure and manipulate their odor response patterns to elucidate their role in pattern decorrelation, volume control, and odor classification. Specifically, we will test the hypothesis that PGCs mediate abrupt switching between discrete sensory representations.3. Differential function of interneurons in Dp (olfactory cortex). Dp contains multiple classes of interneurons that mediate feed-forward and feed-back inhibition. We will use opto- and pharmaco-genetic manipulations of interneurons and 2-photon measurements of activity patterns to test the hypothesis that distinct inhibitory sub-circuits mediate different canonical computations.4. Neuronal circuit function and behavior.We will manipulate interneurons and quantify the effect on circuit functions and odor discrimination learning. Our goal is to test the hypotheses that the discreteness of odor representations in the OB determines the acuity of perception, and that discrimination learning depends on pattern separation/completion in a cortical circuit.Expected value: We expect to uncover general design principles of neuronal circuits that will help to understand relationships between circuit structure, function and dysfunction. Furthermore, we expect to establish direct relationships between neuronal circuit function and defined behaviors. We also expect comparative insights into the organization and function of cortical circuits.
-