Relationship Between Synaptic AMPAR and Spine Dynamics: Impairments in the FXS Mouse

Abstract

Structural dynamics of dendritic spines are important for memory and learning and are impaired in neurodevelopmental disorders such as fragile X syndrome. Spine dynamics are regulated by activity-dependent mechanisms that involve modulation of AMPA receptors (AMPAR); however, the relationship between AMPAR and spine dynamics in vivo and how these are altered in FXS mouse model is not known. Here, we tracked AMPAR and spines over multiple days in vivo in the cortex and found that dendritic spines in the fmr1 KO mouse were denser, smaller, had higher turnover rates and contained less sGluA2 compared to littermate controls. Although, KO spines maintained the relationship between AMPAR and spine stability, AMPAR levels in the KO were more dynamic with larger proportion of spines showing multiple dynamic events of AMPAR. Directional changes in sGluA2 were also observed in newly formed and eliminated spines, with KO spines displaying greater loss of AMPAR before elimination. Thus, we demonstrate that AMPAR levels within spines not are only continuously dynamic, but are also predictive of spine behavior, with impairments observed in the fmr1 KO mice.

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