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High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells

Globular bushy cells (GBCs) of the cochlear nucleus play central roles in the temporal processing of sound. Despite investigation over many decades, fundamental questions remain about their dendrite structure, afferent innervation, and integration of synaptic inputs. Here, we use volume electron mic...

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Autores principales: Spirou, George A, Kersting, Matthew, Carr, Sean, Razzaq, Bayan, Yamamoto Alves Pinto, Carolyna, Dawson, Mariah, Ellisman, Mark H, Manis, Paul B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10435236/
https://www.ncbi.nlm.nih.gov/pubmed/37288824
http://dx.doi.org/10.7554/eLife.83393
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author Spirou, George A
Kersting, Matthew
Carr, Sean
Razzaq, Bayan
Yamamoto Alves Pinto, Carolyna
Dawson, Mariah
Ellisman, Mark H
Manis, Paul B
author_facet Spirou, George A
Kersting, Matthew
Carr, Sean
Razzaq, Bayan
Yamamoto Alves Pinto, Carolyna
Dawson, Mariah
Ellisman, Mark H
Manis, Paul B
author_sort Spirou, George A
collection PubMed
description Globular bushy cells (GBCs) of the cochlear nucleus play central roles in the temporal processing of sound. Despite investigation over many decades, fundamental questions remain about their dendrite structure, afferent innervation, and integration of synaptic inputs. Here, we use volume electron microscopy (EM) of the mouse cochlear nucleus to construct synaptic maps that precisely specify convergence ratios and synaptic weights for auditory nerve innervation and accurate surface areas of all postsynaptic compartments. Detailed biophysically based compartmental models can help develop hypotheses regarding how GBCs integrate inputs to yield their recorded responses to sound. We established a pipeline to export a precise reconstruction of auditory nerve axons and their endbulb terminals together with high-resolution dendrite, soma, and axon reconstructions into biophysically detailed compartmental models that could be activated by a standard cochlear transduction model. With these constraints, the models predict auditory nerve input profiles whereby all endbulbs onto a GBC are subthreshold (coincidence detection mode), or one or two inputs are suprathreshold (mixed mode). The models also predict the relative importance of dendrite geometry, soma size, and axon initial segment length in setting action potential threshold and generating heterogeneity in sound-evoked responses, and thereby propose mechanisms by which GBCs may homeostatically adjust their excitability. Volume EM also reveals new dendritic structures and dendrites that lack innervation. This framework defines a pathway from subcellular morphology to synaptic connectivity, and facilitates investigation into the roles of specific cellular features in sound encoding. We also clarify the need for new experimental measurements to provide missing cellular parameters, and predict responses to sound for further in vivo studies, thereby serving as a template for investigation of other neuron classes.
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spelling pubmed-104352362023-08-18 High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells Spirou, George A Kersting, Matthew Carr, Sean Razzaq, Bayan Yamamoto Alves Pinto, Carolyna Dawson, Mariah Ellisman, Mark H Manis, Paul B eLife Computational and Systems Biology Globular bushy cells (GBCs) of the cochlear nucleus play central roles in the temporal processing of sound. Despite investigation over many decades, fundamental questions remain about their dendrite structure, afferent innervation, and integration of synaptic inputs. Here, we use volume electron microscopy (EM) of the mouse cochlear nucleus to construct synaptic maps that precisely specify convergence ratios and synaptic weights for auditory nerve innervation and accurate surface areas of all postsynaptic compartments. Detailed biophysically based compartmental models can help develop hypotheses regarding how GBCs integrate inputs to yield their recorded responses to sound. We established a pipeline to export a precise reconstruction of auditory nerve axons and their endbulb terminals together with high-resolution dendrite, soma, and axon reconstructions into biophysically detailed compartmental models that could be activated by a standard cochlear transduction model. With these constraints, the models predict auditory nerve input profiles whereby all endbulbs onto a GBC are subthreshold (coincidence detection mode), or one or two inputs are suprathreshold (mixed mode). The models also predict the relative importance of dendrite geometry, soma size, and axon initial segment length in setting action potential threshold and generating heterogeneity in sound-evoked responses, and thereby propose mechanisms by which GBCs may homeostatically adjust their excitability. Volume EM also reveals new dendritic structures and dendrites that lack innervation. This framework defines a pathway from subcellular morphology to synaptic connectivity, and facilitates investigation into the roles of specific cellular features in sound encoding. We also clarify the need for new experimental measurements to provide missing cellular parameters, and predict responses to sound for further in vivo studies, thereby serving as a template for investigation of other neuron classes. eLife Sciences Publications, Ltd 2023-06-08 /pmc/articles/PMC10435236/ /pubmed/37288824 http://dx.doi.org/10.7554/eLife.83393 Text en © 2023, Spirou et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Spirou, George A
Kersting, Matthew
Carr, Sean
Razzaq, Bayan
Yamamoto Alves Pinto, Carolyna
Dawson, Mariah
Ellisman, Mark H
Manis, Paul B
High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells
title High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells
title_full High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells
title_fullStr High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells
title_full_unstemmed High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells
title_short High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells
title_sort high-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10435236/
https://www.ncbi.nlm.nih.gov/pubmed/37288824
http://dx.doi.org/10.7554/eLife.83393
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