UC Santa Cruz

Fragile X syndrome (FXS) is the most common form of genetically inherited mental retardation and although it has been investigated for over 20 years, how cognitive function is specifically disrupted remains unknown. One of the most consistent neuronal phenotypes observed in FXS is increased density of dendritic spines, the protrusions that form postsynaptic components of excitatory synapses. This study further investigates spine abnormalities of the mouse model of FXS in different neuronal compartments, cell types, and cortical regions of wild type and mutant mice, as well as heterozygotes. Increased spine density was identified in mutant mice specifically on apical dendrites of layer 5 neurons. This phenotype only manifests during adulthood and the effect is consistent across multiple sensory regions of the cortex. However, effects on spine density differed between neuronal cell types. These findings identify previously unobserved region, cell type, and cell compartment-specific effects in the mouse model of FXS.