Publications by authors named "Peter Rupprecht"

9 Publications

  • Page 1 of 1

A database and deep learning toolbox for noise-optimized, generalized spike inference from calcium imaging.

Nat Neurosci 2021 09 2;24(9):1324-1337. Epub 2021 Aug 2.

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

Inference of action potentials ('spikes') from neuronal calcium signals is complicated by the scarcity of simultaneous measurements of action potentials and calcium signals ('ground truth'). In this study, we compiled a large, diverse ground truth database from publicly available and newly performed recordings in zebrafish and mice covering a broad range of calcium indicators, cell types and signal-to-noise ratios, comprising a total of more than 35 recording hours from 298 neurons. We developed an algorithm for spike inference (termed CASCADE) that is based on supervised deep networks, takes advantage of the ground truth database, infers absolute spike rates and outperforms existing model-based algorithms. To optimize performance for unseen imaging data, CASCADE retrains itself by resampling ground truth data to match the respective sampling rate and noise level; therefore, no parameters need to be adjusted by the user. In addition, we developed systematic performance assessments for unseen data, openly released a resource toolbox and provide a user-friendly cloud-based implementation.
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http://dx.doi.org/10.1038/s41593-021-00895-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611618PMC
September 2021

Calcium Imaging of CA3 Pyramidal Neuron Populations in Adult Mouse Hippocampus.

eNeuro 2021 Jul-Aug;8(4). Epub 2021 Aug 23.

Laboratory of Neural Circuit Dynamics, Brain Research Institute, University of Zurich, Zurich CH-8057, Switzerland

Neuronal population activity in the hippocampal CA3 subfield is implicated in cognitive brain functions such as memory processing and spatial navigation. However, because of its deep location in the brain, the CA3 area has been difficult to target with modern calcium imaging approaches. Here, we achieved chronic two-photon calcium imaging of CA3 pyramidal neurons with the red fluorescent calcium indicator R-CaMP1.07 in anesthetized and awake mice. We characterize CA3 neuronal activity at both the single-cell and population level and assess its stability across multiple imaging days. During both anesthesia and wakefulness, nearly all CA3 pyramidal neurons displayed calcium transients. Most of the calcium transients were consistent with a high incidence of bursts of action potentials (APs), based on calibration measurements using simultaneous juxtacellular recordings and calcium imaging. In awake mice, we found state-dependent differences with striking large and prolonged calcium transients during locomotion. We estimate that trains of >30 APs over 3 s underlie these salient events. Their abundance in particular subsets of neurons was relatively stable across days. At the population level, we found that co-activity within the CA3 network was above chance level and that co-active neuron pairs maintained their correlated activity over days. Our results corroborate the notion of state-dependent spatiotemporal activity patterns in the recurrent network of CA3 and demonstrate that at least some features of population activity, namely co-activity of cell pairs and likelihood to engage in prolonged high activity, are maintained over days.
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http://dx.doi.org/10.1523/ENEURO.0023-21.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387150PMC
September 2021

A virtual reality system to analyze neural activity and behavior in adult zebrafish.

Nat Methods 2020 03 2;17(3):343-351. Epub 2020 Mar 2.

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

Virtual realities are powerful tools to analyze and manipulate interactions between animals and their environment and to enable measurements of neuronal activity during behavior. In many species, however, optical access to the brain and/or the behavioral repertoire are limited. We developed a high-resolution virtual reality for head-restrained adult zebrafish, which exhibit cognitive behaviors not shown by larvae. We noninvasively measured activity throughout the dorsal telencephalon by multiphoton calcium imaging. Fish in the virtual reality showed regular swimming patterns and were attracted to animations of conspecifics. Manipulations of visuo-motor feedback revealed neurons that responded selectively to the mismatch between the expected and the actual visual consequences of motor output. Such error signals were prominent in multiple telencephalic areas, consistent with models of predictive processing. A virtual reality system for adult zebrafish therefore provides opportunities to analyze neuronal processing mechanisms underlying higher brain functions including decision making, associative learning, and social interactions.
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http://dx.doi.org/10.1038/s41592-020-0759-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100911PMC
March 2020

Precise Synaptic Balance in the Zebrafish Homolog of Olfactory Cortex.

Neuron 2018 11 11;100(3):669-683.e5. Epub 2018 Oct 11.

Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; Faculty of Natural Sciences, University of Basel, 4003 Basel, Switzerland. Electronic address:

Neuronal computations critically depend on the connectivity rules that govern the convergence of excitatory and inhibitory synaptic signals onto individual neurons. To examine the functional synaptic organization of a distributed memory network, we performed voltage clamp recordings in telencephalic area Dp of adult zebrafish, the homolog of olfactory cortex. In neurons of posterior Dp, odor stimulation evoked large, recurrent excitatory and inhibitory inputs that established a transient state of high conductance and synaptic balance. Excitation and inhibition in individual neurons were co-tuned to different odors and correlated on slow and fast timescales. This precise synaptic balance implies specific connectivity among Dp neurons, despite the absence of an obvious topography. Precise synaptic balance stabilizes activity patterns in different directions of coding space and in time while preserving high bandwidth. The coordinated connectivity of excitatory and inhibitory subnetworks in Dp therefore supports fast recurrent memory operations.
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http://dx.doi.org/10.1016/j.neuron.2018.09.013DOI Listing
November 2018

Community-based benchmarking improves spike rate inference from two-photon calcium imaging data.

PLoS Comput Biol 2018 05 21;14(5):e1006157. Epub 2018 May 21.

Center for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.

In recent years, two-photon calcium imaging has become a standard tool to probe the function of neural circuits and to study computations in neuronal populations. However, the acquired signal is only an indirect measurement of neural activity due to the comparatively slow dynamics of fluorescent calcium indicators. Different algorithms for estimating spike rates from noisy calcium measurements have been proposed in the past, but it is an open question how far performance can be improved. Here, we report the results of the spikefinder challenge, launched to catalyze the development of new spike rate inference algorithms through crowd-sourcing. We present ten of the submitted algorithms which show improved performance compared to previously evaluated methods. Interestingly, the top-performing algorithms are based on a wide range of principles from deep neural networks to generative models, yet provide highly correlated estimates of the neural activity. The competition shows that benchmark challenges can drive algorithmic developments in neuroscience.
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http://dx.doi.org/10.1371/journal.pcbi.1006157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997358PMC
May 2018

Experience-Dependent Plasticity of Odor Representations in the Telencephalon of Zebrafish.

Curr Biol 2018 01 14;28(1):1-14.e3. Epub 2017 Dec 14.

Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Basel 4003, Switzerland. Electronic address:

Sensory systems balance stability and plasticity to optimize stimulus representations in dynamic environments. We studied these processes in the olfactory system of adult zebrafish. Activity patterns evoked by repeated odor stimulation were measured by multiphoton calcium imaging in the olfactory bulb (OB) and in telencephalic area Dp, the homolog of olfactory cortex. Whereas odor responses in the OB were highly reproducible, responses of Dp neurons adapted over trials and exhibited substantial variability that could be attributed to ongoing activity and to systematic changes in neuronal representations following each stimulus. An NMDA receptor antagonist did not affect the magnitude of odor responses but strongly reduced the variability and experience-dependent modification of odor responses in Dp. As a consequence, odor representations became stable over trials. These results demonstrate that odor representations in higher brain areas are continuously modified by experience, supporting the view that olfactory processing is inseparable from memory, even in the absence of reinforcement.
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http://dx.doi.org/10.1016/j.cub.2017.11.007DOI Listing
January 2018

Remote z-scanning with a macroscopic voice coil motor for fast 3D multiphoton laser scanning microscopy.

Biomed Opt Express 2016 May 4;7(5):1656-71. Epub 2016 Apr 4.

Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, 4003 Basel, Switzerland.

There is a high demand for 3D multiphoton imaging in neuroscience and other fields but scanning in axial direction presents technical challenges. We developed a focusing technique based on a remote movable mirror that is conjugate to the specimen plane and translated by a voice coil motor. We constructed cost-effective z-scanning modules from off-the-shelf components that can be mounted onto standard multiphoton laser scanning microscopes to extend scan patterns from 2D to 3D. Systems were designed for large objectives and provide high resolution, high speed and a large z-scan range (>300 μm). We used these systems for 3D multiphoton calcium imaging in the adult zebrafish brain and measured odor-evoked activity patterns across >1500 neurons with single-neuron resolution and high signal-to-noise ratio.
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http://dx.doi.org/10.1364/BOE.7.001656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871072PMC
May 2016

Optimizing and extending light-sculpting microscopy for fast functional imaging in neuroscience.

Biomed Opt Express 2015 Feb 8;6(2):353-68. Epub 2015 Jan 8.

Research Institute of Molecular Pathology, Vienna, Austria ; Max F. Perutz Laboratories, University of Vienna, Vienna, Austria ; Research Platform Quantum Phenomena & Nanoscale Biological Systems (QuNaBioS), University of Vienna, Vienna, Austria.

A number of questions in system biology such as understanding how dynamics of neuronal networks are related to brain function require the ability to capture the functional dynamics of large cellular populations at high speed. Recently, this has driven the development of a number of parallel and high speed imaging techniques such as light-sculpting microscopy, which has been used to capture neuronal dynamics at the whole brain and single cell level in small model organisms. However, the broader applicability of light-sculpting microcopy is limited by the size of volumes for which high speed imaging can be obtained and scattering in brain tissue. Here, we present strategies for optimizing the present tradeoffs in light-sculpting microscopy. Various scanning modalities in light-sculpting microscopy are theoretically and experimentally evaluated, and strategies to maximize the obtainable volume speeds, and depth penetration in brain tissue using different laser systems are provided. Design-choices, important parameters and their trade-offs are experimentally demonstrated by performing calcium-imaging in acute mouse-brain slices. We further show that synchronization of line-scanning techniques with rolling-shutter read-out of the camera can reduce scattering effects and enhance image contrast at depth.
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http://dx.doi.org/10.1364/BOE.6.000353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354592PMC
February 2015

A tapered channel microfluidic device for comprehensive cell adhesion analysis, using measurements of detachment kinetics and shear stress-dependent motion.

Biomicrofluidics 2012 Mar 31;6(1):14107-1410712. Epub 2012 Jan 31.

We have developed a method for studying cellular adhesion by using a custom-designed microfluidic device with parallel non-connected tapered channels. The design enables investigation of cellular responses to a large range of shear stress (ratio of 25) with a single input flow-rate. For each shear stress, a large number of cells are analyzed (500-1500 cells), providing statistically relevant data within a single experiment. Besides adhesion strength measurements, the microsystem presented in this paper enables in-depth analysis of cell detachment kinetics by real-time videomicroscopy. It offers the possibility to analyze adhesion-associated processes, such as migration or cell shape change, within the same experiment. To show the versatility of our device, we examined quantitatively cell adhesion by analyzing kinetics, adhesive strength and migration behaviour or cell shape modifications of the unicellular model cell organism Dictyostelium discoideum at 21 °C and of the human breast cancer cell line MDA-MB-231 at 37 °C. For both cell types, we found that the threshold stresses, which are necessary to detach the cells, follow lognormal distributions, and that the detachment process follows first order kinetics. In addition, for particular conditions' cells are found to exhibit similar adhesion threshold stresses, but very different detachment kinetics, revealing the importance of dynamics analysis to fully describe cell adhesion. With its rapid implementation and potential for parallel sample processing, such microsystem offers a highly controllable platform for exploring cell adhesion characteristics in a large set of environmental conditions and cell types, and could have wide applications across cell biology, tissue engineering, and cell screening.
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http://dx.doi.org/10.1063/1.3673802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281936PMC
March 2012
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