Abstract
Alzheimer’s disease (AD), a neurodegenerative disease, causes behavioural abnormalities such as disinhibition, impulsivity, and hyperphagia. Preclinical studies using AD model mice have investigated these phenotypes by measuring brain activity in awake, behaving mice. In this study, we monitored the behavioural alterations of impulsivity and hyperphagia in middle-aged AD model mice. As a behavioural readout, we trained the mice to accept a water-reward under thirsty conditions. To analyse brain activity, we developed a measure for licking behaviour combined with visualisation of whole brain activity using awake fMRI. In a water-reward learning task, the AD model mice showed significant hyperactivity of the dorsal raphe nucleus in thirsty conditions. In summary, we successfully visualised altered brain activity in AD model mice during reward-oriented behaviour for the first time using awake fMRI. This may help in understanding the causes of behavioural alterations in AD patients.
Highlights
Alzheimer’s disease (AD), a neurodegenerative disease, causes behavioural abnormalities such as disinhibition, impulsivity, and hyperphagia
In order to evaluate brain activity of AD model mice during reward-oriented behaviour, in this study, we developed an experimental system for measuring brain activity by Functional magnetic resonance imaging (fMRI) during licking behaviour under thirsty conditions
We developed a paradigm to measure impulsivity in mice, based on an operant learning system that can be applied to awake fMRI (Supplementary Fig. 1)
Summary
Alzheimer’s disease (AD), a neurodegenerative disease, causes behavioural abnormalities such as disinhibition, impulsivity, and hyperphagia. We successfully visualised altered brain activity in AD model mice during reward-oriented behaviour for the first time using awake fMRI. This may help in understanding the causes of behavioural alterations in AD patients. The difference in the functional connectivity between the AD and control mice has been obtained, under these anesthetised conditions, it might not be possible to analyse brain activity during BPSP-associated animal behaviours. In order to evaluate brain activity of AD model mice during reward-oriented behaviour, in this study, we developed an experimental system for measuring brain activity by fMRI during licking behaviour under thirsty conditions. To identify the neurological mechanisms underlying BPSP in AD, imaging was performed using ultra-high field MRI (14 T) on mice to ensure the best possible trade-off for small animals[15]
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