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Normalized unitary synaptic signaling of the hippocampus and entorhinal cortex predicted by deep learning of experimental recordings

Biologically realistic computer simulations of neuronal circuits require systematic data-driven modeling of neuron type-specific synaptic activity. However, limited experimental yield, heterogeneous recordings conditions, and ambiguous neuronal identification have so far prevented the consistent cha...

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Autores principales: Moradi, Keivan, Aldarraji, Zainab, Luthra, Megha, Madison, Grey P., Ascoli, Giorgio A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072429/
https://www.ncbi.nlm.nih.gov/pubmed/35513471
http://dx.doi.org/10.1038/s42003-022-03329-5
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author Moradi, Keivan
Aldarraji, Zainab
Luthra, Megha
Madison, Grey P.
Ascoli, Giorgio A.
author_facet Moradi, Keivan
Aldarraji, Zainab
Luthra, Megha
Madison, Grey P.
Ascoli, Giorgio A.
author_sort Moradi, Keivan
collection PubMed
description Biologically realistic computer simulations of neuronal circuits require systematic data-driven modeling of neuron type-specific synaptic activity. However, limited experimental yield, heterogeneous recordings conditions, and ambiguous neuronal identification have so far prevented the consistent characterization of synaptic signals for all connections of any neural system. We introduce a strategy to overcome these challenges and report a comprehensive synaptic quantification among all known neuron types of the hippocampal-entorhinal network. First, we reconstructed >2600 synaptic traces from ∼1200 publications into a unified computational representation of synaptic dynamics. We then trained a deep learning architecture with the resulting parameters, each annotated with detailed metadata such as recording method, solutions, and temperature. The model learned to predict the synaptic properties of all 3,120 circuit connections in arbitrary conditions with accuracy approaching the intrinsic experimental variability. Analysis of data normalized and completed with the deep learning model revealed that synaptic signals are controlled by few latent variables associated with specific molecular markers and interrelating conductance, decay time constant, and short-term plasticity. We freely release the tools and full dataset of unitary synaptic values in 32 covariate settings. Normalized synaptic data can be used in brain simulations, and to predict and test experimental hypothesis.
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spelling pubmed-90724292022-05-07 Normalized unitary synaptic signaling of the hippocampus and entorhinal cortex predicted by deep learning of experimental recordings Moradi, Keivan Aldarraji, Zainab Luthra, Megha Madison, Grey P. Ascoli, Giorgio A. Commun Biol Article Biologically realistic computer simulations of neuronal circuits require systematic data-driven modeling of neuron type-specific synaptic activity. However, limited experimental yield, heterogeneous recordings conditions, and ambiguous neuronal identification have so far prevented the consistent characterization of synaptic signals for all connections of any neural system. We introduce a strategy to overcome these challenges and report a comprehensive synaptic quantification among all known neuron types of the hippocampal-entorhinal network. First, we reconstructed >2600 synaptic traces from ∼1200 publications into a unified computational representation of synaptic dynamics. We then trained a deep learning architecture with the resulting parameters, each annotated with detailed metadata such as recording method, solutions, and temperature. The model learned to predict the synaptic properties of all 3,120 circuit connections in arbitrary conditions with accuracy approaching the intrinsic experimental variability. Analysis of data normalized and completed with the deep learning model revealed that synaptic signals are controlled by few latent variables associated with specific molecular markers and interrelating conductance, decay time constant, and short-term plasticity. We freely release the tools and full dataset of unitary synaptic values in 32 covariate settings. Normalized synaptic data can be used in brain simulations, and to predict and test experimental hypothesis. Nature Publishing Group UK 2022-05-05 /pmc/articles/PMC9072429/ /pubmed/35513471 http://dx.doi.org/10.1038/s42003-022-03329-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Moradi, Keivan
Aldarraji, Zainab
Luthra, Megha
Madison, Grey P.
Ascoli, Giorgio A.
Normalized unitary synaptic signaling of the hippocampus and entorhinal cortex predicted by deep learning of experimental recordings
title Normalized unitary synaptic signaling of the hippocampus and entorhinal cortex predicted by deep learning of experimental recordings
title_full Normalized unitary synaptic signaling of the hippocampus and entorhinal cortex predicted by deep learning of experimental recordings
title_fullStr Normalized unitary synaptic signaling of the hippocampus and entorhinal cortex predicted by deep learning of experimental recordings
title_full_unstemmed Normalized unitary synaptic signaling of the hippocampus and entorhinal cortex predicted by deep learning of experimental recordings
title_short Normalized unitary synaptic signaling of the hippocampus and entorhinal cortex predicted by deep learning of experimental recordings
title_sort normalized unitary synaptic signaling of the hippocampus and entorhinal cortex predicted by deep learning of experimental recordings
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072429/
https://www.ncbi.nlm.nih.gov/pubmed/35513471
http://dx.doi.org/10.1038/s42003-022-03329-5
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