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Amyloid pathology impairs experience-dependent inhibitory synaptic plasticity
Alzheimer’s disease patients and mouse models exhibit aberrant neuronal activity and altered excitatory-to-inhibitory synaptic ratio. Using multicolor two-photon microscopy, we test how amyloid pathology alters the structural dynamics of excitatory and inhibitory synapses and their adaptation to alt...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10187277/ https://www.ncbi.nlm.nih.gov/pubmed/37205469 http://dx.doi.org/10.1101/2023.05.04.539450 |
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author | Niraula, Suraj Yan, Shirley ShiDu Subramanian, Jaichandar |
author_facet | Niraula, Suraj Yan, Shirley ShiDu Subramanian, Jaichandar |
author_sort | Niraula, Suraj |
collection | PubMed |
description | Alzheimer’s disease patients and mouse models exhibit aberrant neuronal activity and altered excitatory-to-inhibitory synaptic ratio. Using multicolor two-photon microscopy, we test how amyloid pathology alters the structural dynamics of excitatory and inhibitory synapses and their adaptation to altered visual experience in vivo in the visual cortex. We show that the baseline dynamics of mature excitatory synapses and their adaptation to visual deprivation are not altered in amyloidosis. Likewise, the baseline dynamics of inhibitory synapses are not affected. In contrast, visual deprivation fails to induce inhibitory synapse loss in amyloidosis, a phenomenon observed in nonpathological conditions. Intriguingly, inhibitory synapse loss associated with visual deprivation in nonpathological mice is accompanied by the broadening of spontaneous but not visually evoked calcium transients. However, such broadening does not manifest in the context of amyloidosis. We also show that excitatory and inhibitory synapse loss is locally clustered under the nonpathological state. In contrast, a fraction of synapse loss is not locally clustered in amyloidosis, indicating an impairment in inhibitory synapse adaptation to changes in excitatory synaptic activity. |
format | Online Article Text |
id | pubmed-10187277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-101872772023-05-17 Amyloid pathology impairs experience-dependent inhibitory synaptic plasticity Niraula, Suraj Yan, Shirley ShiDu Subramanian, Jaichandar bioRxiv Article Alzheimer’s disease patients and mouse models exhibit aberrant neuronal activity and altered excitatory-to-inhibitory synaptic ratio. Using multicolor two-photon microscopy, we test how amyloid pathology alters the structural dynamics of excitatory and inhibitory synapses and their adaptation to altered visual experience in vivo in the visual cortex. We show that the baseline dynamics of mature excitatory synapses and their adaptation to visual deprivation are not altered in amyloidosis. Likewise, the baseline dynamics of inhibitory synapses are not affected. In contrast, visual deprivation fails to induce inhibitory synapse loss in amyloidosis, a phenomenon observed in nonpathological conditions. Intriguingly, inhibitory synapse loss associated with visual deprivation in nonpathological mice is accompanied by the broadening of spontaneous but not visually evoked calcium transients. However, such broadening does not manifest in the context of amyloidosis. We also show that excitatory and inhibitory synapse loss is locally clustered under the nonpathological state. In contrast, a fraction of synapse loss is not locally clustered in amyloidosis, indicating an impairment in inhibitory synapse adaptation to changes in excitatory synaptic activity. Cold Spring Harbor Laboratory 2023-09-30 /pmc/articles/PMC10187277/ /pubmed/37205469 http://dx.doi.org/10.1101/2023.05.04.539450 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Niraula, Suraj Yan, Shirley ShiDu Subramanian, Jaichandar Amyloid pathology impairs experience-dependent inhibitory synaptic plasticity |
title | Amyloid pathology impairs experience-dependent inhibitory synaptic plasticity |
title_full | Amyloid pathology impairs experience-dependent inhibitory synaptic plasticity |
title_fullStr | Amyloid pathology impairs experience-dependent inhibitory synaptic plasticity |
title_full_unstemmed | Amyloid pathology impairs experience-dependent inhibitory synaptic plasticity |
title_short | Amyloid pathology impairs experience-dependent inhibitory synaptic plasticity |
title_sort | amyloid pathology impairs experience-dependent inhibitory synaptic plasticity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10187277/ https://www.ncbi.nlm.nih.gov/pubmed/37205469 http://dx.doi.org/10.1101/2023.05.04.539450 |
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