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A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease

Alzheimer’s Disease (AD) is characterized by progressive neurodegeneration and cognitive impairment. Synaptic dysfunction is an established early symptom, which correlates strongly with cognitive decline, and is hypothesised to mediate the diverse neuronal network abnormalities observed in AD. Howev...

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Detalles Bibliográficos
Autores principales: Ness, Natalie, Schultz, Simon R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238223/
https://www.ncbi.nlm.nih.gov/pubmed/34133417
http://dx.doi.org/10.1371/journal.pcbi.1009115
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author Ness, Natalie
Schultz, Simon R.
author_facet Ness, Natalie
Schultz, Simon R.
author_sort Ness, Natalie
collection PubMed
description Alzheimer’s Disease (AD) is characterized by progressive neurodegeneration and cognitive impairment. Synaptic dysfunction is an established early symptom, which correlates strongly with cognitive decline, and is hypothesised to mediate the diverse neuronal network abnormalities observed in AD. However, how synaptic dysfunction contributes to network pathology and cognitive impairment in AD remains elusive. Here, we present a grid-cell-to-place-cell transformation model of long-term CA1 place cell dynamics to interrogate the effect of synaptic loss on network function and environmental representation. Synapse loss modelled after experimental observations in the APP/PS1 mouse model was found to induce firing rate alterations and place cell abnormalities that have previously been observed in AD mouse models, including enlarged place fields and lower across-session stability of place fields. Our results support the hypothesis that synaptic dysfunction underlies cognitive deficits, and demonstrate how impaired environmental representation may arise in the early stages of AD. We further propose that dysfunction of excitatory and inhibitory inputs to CA1 pyramidal cells may cause distinct impairments in place cell function, namely reduced stability and place map resolution.
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spelling pubmed-82382232021-07-09 A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease Ness, Natalie Schultz, Simon R. PLoS Comput Biol Research Article Alzheimer’s Disease (AD) is characterized by progressive neurodegeneration and cognitive impairment. Synaptic dysfunction is an established early symptom, which correlates strongly with cognitive decline, and is hypothesised to mediate the diverse neuronal network abnormalities observed in AD. However, how synaptic dysfunction contributes to network pathology and cognitive impairment in AD remains elusive. Here, we present a grid-cell-to-place-cell transformation model of long-term CA1 place cell dynamics to interrogate the effect of synaptic loss on network function and environmental representation. Synapse loss modelled after experimental observations in the APP/PS1 mouse model was found to induce firing rate alterations and place cell abnormalities that have previously been observed in AD mouse models, including enlarged place fields and lower across-session stability of place fields. Our results support the hypothesis that synaptic dysfunction underlies cognitive deficits, and demonstrate how impaired environmental representation may arise in the early stages of AD. We further propose that dysfunction of excitatory and inhibitory inputs to CA1 pyramidal cells may cause distinct impairments in place cell function, namely reduced stability and place map resolution. Public Library of Science 2021-06-16 /pmc/articles/PMC8238223/ /pubmed/34133417 http://dx.doi.org/10.1371/journal.pcbi.1009115 Text en © 2021 Ness, Schultz https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ness, Natalie
Schultz, Simon R.
A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease
title A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease
title_full A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease
title_fullStr A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease
title_full_unstemmed A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease
title_short A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease
title_sort computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage alzheimer’s disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238223/
https://www.ncbi.nlm.nih.gov/pubmed/34133417
http://dx.doi.org/10.1371/journal.pcbi.1009115
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