TY - JOUR
T1 - Disrupted theta synchronization and synaptic connectivity in the visual cortex of Fmr1 KO mice
AU - Cheng, Xi
AU - Nareddula, Sanghamitra
AU - Gao, Hao Cheng
AU - Chen, Yueyi
AU - Xiao, Tiange
AU - Nadew, Yididiya Y.
AU - Xu, Fan
AU - Edens, Paige Alyssa
AU - Saldarriaga, Violeta
AU - Hu, Xinwan
AU - Quinn, Christopher J.
AU - Kimbrough, Adam
AU - Huang, Fang
AU - Chubykin, Alexander A.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Fragile X syndrome (FX) is a leading inherited cause of autism spectrum disorder, characterized by sensory hypersensitivity and impaired visual learning. Visual experience induces synchronized theta oscillations in the primary visual cortex (V1) and lateromedial area (LM), supporting inter-areal sensory binding. Using the Fmr1 knockout (KO) mouse model of FX, we quantify experience-dependent c-Fos expression in V1 and LM via iDISCO whole-brain clearing. Simultaneous in vivo recordings and channelrhodopsin-2-assisted circuit mapping (CRACM) reveal synchronized V1–LM theta oscillations and strengthened feedforward V1 → LM connectivity in wild-type (WT) mice, but attenuated LM oscillations and impaired connectivity in FX mice. Using 4Pi single-molecule localization microscopy, we identify experience-driven dendritic spine remodeling in layer 5 pyramidal cells of V1 and LM in WT mice, which is absent in FX mice. FX mice also show elevated baseline spine density and length. Our findings demonstrate that visual experience drives inter-areal synchronization and synaptic plasticity, which are disrupted in FX.
AB - Fragile X syndrome (FX) is a leading inherited cause of autism spectrum disorder, characterized by sensory hypersensitivity and impaired visual learning. Visual experience induces synchronized theta oscillations in the primary visual cortex (V1) and lateromedial area (LM), supporting inter-areal sensory binding. Using the Fmr1 knockout (KO) mouse model of FX, we quantify experience-dependent c-Fos expression in V1 and LM via iDISCO whole-brain clearing. Simultaneous in vivo recordings and channelrhodopsin-2-assisted circuit mapping (CRACM) reveal synchronized V1–LM theta oscillations and strengthened feedforward V1 → LM connectivity in wild-type (WT) mice, but attenuated LM oscillations and impaired connectivity in FX mice. Using 4Pi single-molecule localization microscopy, we identify experience-driven dendritic spine remodeling in layer 5 pyramidal cells of V1 and LM in WT mice, which is absent in FX mice. FX mice also show elevated baseline spine density and length. Our findings demonstrate that visual experience drives inter-areal synchronization and synaptic plasticity, which are disrupted in FX.
UR - https://www.scopus.com/pages/publications/105023090383
U2 - 10.1038/s41467-025-65665-4
DO - 10.1038/s41467-025-65665-4
M3 - Article
C2 - 41298434
AN - SCOPUS:105023090383
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 10583
ER -