Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1785092054179643392 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10435236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT spirougeorgea highresolutionvolumetricimagingconstrainscompartmentalmodelstoexploresynapticintegrationandtemporalprocessingbycochlearnucleusglobularbushycells AT kerstingmatthew highresolutionvolumetricimagingconstrainscompartmentalmodelstoexploresynapticintegrationandtemporalprocessingbycochlearnucleusglobularbushycells AT carrsean highresolutionvolumetricimagingconstrainscompartmentalmodelstoexploresynapticintegrationandtemporalprocessingbycochlearnucleusglobularbushycells AT razzaqbayan highresolutionvolumetricimagingconstrainscompartmentalmodelstoexploresynapticintegrationandtemporalprocessingbycochlearnucleusglobularbushycells AT yamamotoalvespintocarolyna highresolutionvolumetricimagingconstrainscompartmentalmodelstoexploresynapticintegrationandtemporalprocessingbycochlearnucleusglobularbushycells AT dawsonmariah highresolutionvolumetricimagingconstrainscompartmentalmodelstoexploresynapticintegrationandtemporalprocessingbycochlearnucleusglobularbushycells AT ellismanmarkh highresolutionvolumetricimagingconstrainscompartmentalmodelstoexploresynapticintegrationandtemporalprocessingbycochlearnucleusglobularbushycells AT manispaulb highresolutionvolumetricimagingconstrainscompartmentalmodelstoexploresynapticintegrationandtemporalprocessingbycochlearnucleusglobularbushycells |