Neuronal circuit; Interneuron; Optogenetics; Olfactory bulb; Olfactory cortex; Zebrafish; Neuronal computation
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.
Friedrich Rainer W, Wiechert Martin T (2014), Neuronal circuits and computations: pattern decorrelation in the olfactory bulb., in FEBS letters
, 588(15), 2504-13.
Friedrich Rainer W, Moressis Anastasios, Frank Thomas (2014), Stereotopy versus stochasticity in olfaction., in Nature neuroscience
, 17(2), 147-9.
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.
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.
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.
Jacobson Gilad A., Friedrich Rainer W. (2013), Neural Circuits: Random Design of a Higher-Order Olfactory Projection, in CURRENT BIOLOGY
, 23(10), 448-451.
Friedrich Rainer W (2013), Neuronal computations in the olfactory system of zebrafish., in Annual review of neuroscience
, 36, 383-402.
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.
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.
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.
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.
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.