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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Vydáno v:PLoS computational biology Ročník 17; číslo 6; s. e1009115
Hlavní autoři: Ness, Natalie, Schultz, Simon R.
Médium: Journal Article
Jazyk:angličtina
Vydáno: San Francisco Public Library of Science 16.06.2021
Public Library of Science (PLoS)
Témata:
Abnormalities
Alzheimer's disease
Animal models
Biology and Life Sciences
Cognitive ability
Competition
Computational grids
Computational neuroscience
Development and progression
Feedback
Firing rate
Health aspects
Impairment
Medicine and Health Sciences
Memory
Neurodegeneration
Neurodegenerative diseases
Presenilin 1
Pyramidal cells
Representations
Research and Analysis Methods
Simulation
Stability
Synapses
Transformation
Transformations (mathematics)
United Kingdom
ISSN:1553-7358, 1553-734X, 1553-7358
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Popis
Shrnutí: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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The authors have declared that no competing interests exist.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1009115