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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...

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Autores principales: Niraula, Suraj, Yan, Shirley ShiDu, Subramanian, Jaichandar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
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.
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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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