5XFAD mice show early-onset gap encoding deficits in the auditory cortex

NEUROBIOLOGY OF AGING

卷:94

Article

Weible, Aldis P.¹  Stebritz, Amanda J.¹  Wehr, Michael¹ 

[1] Inst Neurosci, Dept Psychol, 1254 Univ Oregon, Eugene, OR 97403 USA

关键词: Gap detection;    Temporal processing;    Auditory cortex;    5XFAD;    Biomarker;   

DOI  :  10.1016/j.neurobiolaging.2020.05.013

来源: Elsevier

【 摘 要 】

Early detection will be crucial for effective treatment or prevention of Alzheimer's disease. The identification and validation of early, noninvasive biomarkers is therefore key to avoiding the most devastating aspects of Alzheimer's disease. Measures of central auditory processing such as gap detection have recently emerged as potential biomarkers in both human patients and the 5XFAD mouse model of Alzheimer's disease. Full validation of gap detection deficits as a biomarker will require detailed understanding of the underlying neuropathology, including which brain structures are involved and how the operation of neural circuits is affected. Here we show that 5XFAD mice exhibit gap detection deficits as early as 2 months of age, well before development of Alzheimer's disease-associated pathology. We then examined responses of neurons in the auditory cortex to gaps in white noise. Both gap responses and baseline firing rates were robustly and progressively degraded in 5XFAD mice compared to litter mate controls. These impairments were first evident at 2-4 months of age in males, and 4-6 months in females. This demonstrates early-onset impairments to the central auditory system, which could be due to damage in the auditory cortex, upstream subcortical structures, or both. (C) 2020 Elsevier Inc. All rights reserved.

【 授权许可】

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