title: Inference of neuronal network spike dynamics and topology from calcium imaging data.
abstract: Two-photon calcium imaging enables functional analysis of neuronal circuits by inferring action potential (AP) occurrence ("spike trains") from cellular fluorescence signals. It remains unclear how experimental parameters such as signal-to-noise ratio (SNR) and acquisition rate affect spike inference and whether additional information about network structure can be extracted. Here we present a simulation framework for quantitatively assessing how well spike dynamics and network topology can be inferred from noisy calcium imaging data. For simulated AP-evoked calcium transients in neocortical pyramidal cells, we analyzed the quality of spike inference as a function of SNR and data acquisition rate using a recently introduced peeling algorithm. Given experimentally attainable values of SNR and acquisition rate, neural spike trains could be reconstructed accurately and with up to millisecond precision. We then applied statistical neuronal network models to explore how remaining uncertainties in spike inference affect estimates of network connectivity and topological features of network organization. We define the experimental conditions suitable for inferring whether the network has a scale-free structure and determine how well hub neurons can be identified. Our findings provide a benchmark for future calcium imaging studies that aim to reliably infer neuronal network properties.
authors.affiliation: Laboratory of Neural Circuit Dynamics, Brain Research Institute, University of Zurich Zurich, Switzerland.
authors.forename: Henry
authors.initials: H
authors.lastname: Lütcke
authors.affiliation: School of Computer and Communication Sciences and School of Life Sciences, Brain-Mind Institute, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Felipe
authors.initials: F
authors.lastname: Gerhard
authors.affiliation: School of Computer and Communication Sciences and School of Life Sciences, Brain-Mind Institute, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Zenke
authors.affiliation: School of Computer and Communication Sciences and School of Life Sciences, Brain-Mind Institute, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
authors.forename: Wulfram
authors.initials: W
authors.lastname: Gerstner
authors.affiliation: Laboratory of Neural Circuit Dynamics, Brain Research Institute, University of Zurich Zurich, Switzerland ; Neuroscience Center Zurich, University of Zurich and ETH Zurich Zurich, Switzerland.
authors.forename: Fritjof
authors.initials: F
authors.lastname: Helmchen
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000465:Algorithms; D002118:Calcium / Q000378:metabolism*; D003198:Computer Simulation; D036641:Microscopy, Fluorescence, Multiphoton; D008959:Models, Neurological; D009415:Nerve Net / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D059629:Signal-To-Noise Ratio
chemical_list: D002118:Calcium
keywords: action potential; calcium; connectivity; hub neurons; reconstruction; scale-free