Functional connectivity favors aberrant visual network c-Fos expression accompanied by cortical synapse loss in amyloidosis

Abstract

AbstractWhile Alzheimer’s disease (AD) has been extensively studied with a focus on cognitive networks, sensory network dysfunction has received comparatively less attention despite compelling evidence of its significance in both Alzheimer’s disease patients and mouse models. We recently found that neurons in the primary visual cortex of an amyloid mouse model exhibit an imbalance of postsynaptic structures favoring neuronal hyperactivity alongside increased c-Fos expression, which regulates plasticity and memory. Here, we investigate aberrant visual network and brain-wide c-Fos expression and functional connectivity patterns, network responses to light deprivation, and visual system presynaptic deficits of a mouse model of Alzheimer’s disease. We found that the mouse model of AD exhibits aberrant c-Fos expression and functional connectivity patterns across multiple brain regions, and functional connectivity between brain regions is a significant predictor for aberrant c-Fos expression. We also show that one week of light deprivation increases c-Fos expression across the brain in nonpathological controls but not the AD model, indicating experience-dependent plasticity deficits in multiple brain regions. Usingin vivoandex vivoimaging of presynaptic termini, we found that aberrant visual cortical c-Fos expression is associated with selective loss of excitatory cortical but not inhibitory or subcortical synapses. Our findings reveal novel structural and functional connectivity deficits in the visual network pre-plaque amyloidosis.