%0 Journal Article
%T Functional Connectivity Favors Aberrant Visual Network c-Fos Expression Accompanied by Cortical Synapse Loss in a Mouse Model of Alzheimer's Disease.
%A L'Esperance OJ
%A McGhee J
%A Davidson G
%A Niraula S
%A Smith AS
%A Sosunov AA
%A Yan SS
%A Subramanian J
%J J Alzheimers Dis
%V 101
%N 1
%D 2024 Aug 7
%M 39121131
%F 4.16
%R 10.3233/JAD-240776
%X <B>UNASSIGNED: </B>While Alzheimer's disease (AD) has been extensively studied with a focus on cognitive networks, visual network dysfunction has received less attention despite compelling evidence of its significance in AD patients and mouse models. We recently reported c-Fos and synaptic dysregulation in the primary visual cortex of a pre-amyloid plaque AD-model.<BR><B>UNASSIGNED: </B>We test whether c-Fos expression and presynaptic density/dynamics differ in cortical and subcortical visual areas in an AD-model. We also examine whether aberrant c-Fos expression is inherited through functional connectivity and shaped by light experience.<BR><B>UNASSIGNED: </B>c-Fos+ cell density, functional connectivity, and their experience-dependent modulation were assessed for visual and whole-brain networks in both sexes of 4-6-month-old J20 (AD-model) and wildtype (WT) mice. Cortical and subcortical differences in presynaptic vulnerability in the AD-model were compared using ex vivo and in vivo imaging.<BR><B>UNASSIGNED: </B>Visual cortical, but not subcortical, networks show aberrant c-Fos expression and impaired experience-dependent modulation. The average functional connectivity of a brain region in WT mice significantly predicts aberrant c-Fos expression, which correlates with impaired experience-dependent modulation in the AD-model. We observed a subtle yet selective weakening of excitatory visual cortical synapses. The size distribution of cortical boutons in the AD-model is downscaled relative to those in WT mice, suggesting a synaptic scaling-like adaptation of bouton size.<BR><B>UNASSIGNED: </B>Visual network structural and functional disruptions are biased toward cortical regions in pre-plaque J20 mice, and the cellular and synaptic dysregulation in the AD-model represents a maladaptive modification of the baseline physiology seen in WT conditions.