Claire Guerrier, Tristan Dellazizzo Toth, Nicolas Galtier, Kurt Haas
{"title":"An Algorithm Based on a Cable-Nernst Planck Model Predicting Synaptic Activity throughout the Dendritic Arbor with Micron Specificity.","authors":"Claire Guerrier, Tristan Dellazizzo Toth, Nicolas Galtier, Kurt Haas","doi":"10.1007/s12021-022-09609-z","DOIUrl":null,"url":null,"abstract":"<p><p>Recent technological advances have enabled the recording of neurons in intact circuits with a high spatial and temporal resolution, creating the need for modeling with the same precision. In particular, the development of ultra-fast two-photon microscopy combined with fluorescence-based genetically-encoded Ca<sup>2+</sup>-indicators allows capture of full-dendritic arbor and somatic responses associated with synaptic input and action potential output. The complexity of dendritic arbor structures and distributed patterns of activity over time results in the generation of incredibly rich 4D datasets that are challenging to analyze (Sakaki et al. in Frontiers in Neural Circuits 14:33, 2020). Interpreting neural activity from fluorescence-based Ca<sup>2+</sup> biosensors is challenging due to non-linear interactions between several factors influencing intracellular calcium ion concentration and its binding to sensors, including the ionic dynamics driven by diffusion, electrical gradients and voltage-gated conductances. To investigate those dynamics, we designed a model based on a Cable-like equation coupled to the Nernst-Planck equations for ionic fluxes in electrolytes. We employ this model to simulate signal propagation and ionic electrodiffusion across a dendritic arbor. Using these simulation results, we then designed an algorithm to detect synapses from Ca<sup>2+</sup> imaging datasets. We finally apply this algorithm to experimental Ca<sup>2+</sup>-indicator datasets from neurons expressing jGCaMP7s (Dana et al. in Nature Methods 16:649-657, 2019), using full-dendritic arbor sampling in vivo in the Xenopus laevis optic tectum using fast random-access two-photon microscopy. Our model reproduces the dynamics of visual stimulus-evoked jGCaMP7s-mediated calcium signals observed experimentally, and the resulting algorithm allows prediction of the location of synapses across the dendritic arbor. Our study provides a way to predict synaptic activity and location on dendritic arbors, from fluorescence data in the full dendritic arbor of a neuron recorded in the intact and awake developing vertebrate brain.</p>","PeriodicalId":49761,"journal":{"name":"Neuroinformatics","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroinformatics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12021-022-09609-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS","Score":null,"Total":0}
引用次数: 0
Abstract
Recent technological advances have enabled the recording of neurons in intact circuits with a high spatial and temporal resolution, creating the need for modeling with the same precision. In particular, the development of ultra-fast two-photon microscopy combined with fluorescence-based genetically-encoded Ca2+-indicators allows capture of full-dendritic arbor and somatic responses associated with synaptic input and action potential output. The complexity of dendritic arbor structures and distributed patterns of activity over time results in the generation of incredibly rich 4D datasets that are challenging to analyze (Sakaki et al. in Frontiers in Neural Circuits 14:33, 2020). Interpreting neural activity from fluorescence-based Ca2+ biosensors is challenging due to non-linear interactions between several factors influencing intracellular calcium ion concentration and its binding to sensors, including the ionic dynamics driven by diffusion, electrical gradients and voltage-gated conductances. To investigate those dynamics, we designed a model based on a Cable-like equation coupled to the Nernst-Planck equations for ionic fluxes in electrolytes. We employ this model to simulate signal propagation and ionic electrodiffusion across a dendritic arbor. Using these simulation results, we then designed an algorithm to detect synapses from Ca2+ imaging datasets. We finally apply this algorithm to experimental Ca2+-indicator datasets from neurons expressing jGCaMP7s (Dana et al. in Nature Methods 16:649-657, 2019), using full-dendritic arbor sampling in vivo in the Xenopus laevis optic tectum using fast random-access two-photon microscopy. Our model reproduces the dynamics of visual stimulus-evoked jGCaMP7s-mediated calcium signals observed experimentally, and the resulting algorithm allows prediction of the location of synapses across the dendritic arbor. Our study provides a way to predict synaptic activity and location on dendritic arbors, from fluorescence data in the full dendritic arbor of a neuron recorded in the intact and awake developing vertebrate brain.
期刊介绍:
Neuroinformatics publishes original articles and reviews with an emphasis on data structure and software tools related to analysis, modeling, integration, and sharing in all areas of neuroscience research. The editors particularly invite contributions on: (1) Theory and methodology, including discussions on ontologies, modeling approaches, database design, and meta-analyses; (2) Descriptions of developed databases and software tools, and of the methods for their distribution; (3) Relevant experimental results, such as reports accompanie by the release of massive data sets; (4) Computational simulations of models integrating and organizing complex data; and (5) Neuroengineering approaches, including hardware, robotics, and information theory studies.