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. Author manuscript; available in PMC: 2014 Oct 22.
Published in final edited form as: Neuroscience. 2012 Apr 20;251:120–128. doi: 10.1016/j.neuroscience.2012.03.049

Figure 2. Possible mechanisms to explain spine defects in fragile X syndrome.

Figure 2

These cartoons depict the various dendritic spine defects that have been reported or proposed in patients with FXS or in Fmr1 KO mice, as well as the theories that may bring about those defects.

(a) Spine maturation and plasticity in wild type mice. During early brain development dendrites are studded with headless protrusions called filopodia. These are highly motile and transient protrusions that play a role in early synaptogenesis. In the adult, dendritic spines can be classified morphologically into three main types: thin, stuffy and mushroom. Thin spines tend to be smaller and have shorter lifetimes (days), whereas mushroom spines tend to be the largest and most stable (weeks to months). Spines are plastic structures such that changes in network activity (e.g., sensory inputs, learning new tasks) can modify the size, shape and turnover to influence synaptic strength (e.g., experience-dependent plasticity, LTP).

(b) Spine maturation and plasticity in fragile X syndrome. An over-production of spines (or a failure to prune them after development) can lead to a higher spine density as reported in some studies of Fmr1 KO mice. Alternatively, a delayed maturation of dendritic protrusions results in an overabundance of spines with immature morphologies or higher than normal turnover. In addition, spines in FXS may exhibit defects in activity-dependent plasticity.

Potential consequences of a higher spine density on the network might include seizures or an exaggerated response to sensory stimuli due to hyperconnectivity. Potential consequences of having immature spines (delayed stabilization and/or immature morphology) might include problems with learning and memory consolidation, due to a reduction in synapse number or to the formation of weaker, short-lasting synapses. Portential consequences of failure of spines to exhibit normal plasticity (e.g., experience-dependent plasticity) would also include problems with learning and memory, as well as sensory integration defects.