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Functional activity alterations are one of the earliest hallmarks of Alzheimer's disease (AD), already detected prior to beta-amyloid plaque and tau-tangle accumulation. To reveal the physiological basis underpinning these changes at the onset of the pathology, we leveraged fMRI in the 3xTgAD mouse model for AD. Resting-state fMRI revealed functional connectivity loss within areas homologous to the human temporal lobe, particularly the entorhinal cortex. Optogenetic activation of the entorhinaldoi:10.1101/2020.04.03.022590 fatcat:t6lwetdlezerrg5ed7a6jkkc5e