Investigating dendritic spine abnormalities within layer V cerebral cortical neurons of fmr1 heterozygous mouse models
Mutation in the Fmr1 gene is widely accepted as the functional cause of Fragile X syndrome (FXS). As FXS is an X-linked chromosomal disorder, previous studies have focused on male Fmr1 knockouts (KO) since they present the most severe form of this disorder. Within FXS patients, dendritic spines display abnormalities in their type and density. This effect is paralleled in Fmr1 KO model mice. Previous literature has suggested a role for both pre-synaptic and astrocytic Fragile X Mental Retardation Protein (FMRP) within the brain, but less is known regarding the post-synaptic function of FMRP. Even less is known about the role of FMRP in female Fmr1 heterozygotes (HET). Using Fmr1 mosaic models, we tested the hypothesis that FMRP may play a post-synaptic role in the development of dendritic spine density and type within layer V pyramidal neurons of mouse primary sensory areas of the cerebral cortex. Fmr1 HET layer V pyramidal neurons were labeled by crossing mice with the Thy1 GFP-M line. Immunohistochemistry was used to determine the FMRP expression of individual cells within the mosaic brain. Dendritic spine density was then analyzed proximal to the primary branch point of the apical dendrite. Results revealed that Fmr1 HETs display elevated dendritic spine densities compared to wildtype (WT) mice; however, in Fmr1 HET brains, post-synaptic FMRP identity was not correlated with a change in dendritic spine type or density. Thus, it is likely that, if FMRP plays a post-synaptic role in addition to its astrocytic and pre-synaptic roles, it is non-cell autonomous.