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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.
Ness, Natalie; Schultz, Simon R.
Afiliación
  • Ness N; Centre for Neurotechnology and Department of Bioengineering, Imperial College London, London, United Kingdom.
  • Schultz SR; Centre for Neurotechnology and Department of Bioengineering, Imperial College London, London, United Kingdom.
PLoS Comput Biol ; 17(6): e1009115, 2021 06.
Article en En | MEDLINE | ID: mdl-34133417
ABSTRACT
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Modelos Neurológicos Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: PLoS Comput Biol Asunto de la revista: BIOLOGIA / INFORMATICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer / Modelos Neurológicos Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: PLoS Comput Biol Asunto de la revista: BIOLOGIA / INFORMATICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Reino Unido