The role of the dorsal striatum in a mouse model for fragile X syndrome: Behavioral and dendritic spine assessment. Academic Article uri icon


  • Fragile X syndrome (FXS), a leading monogenic cause of autism spectrum disorders (ASDs), typically occurs as the result of a mutation silencing the Fmr1 gene, preventing production of the fragile X messenger ribonucleoprotein (FMRP). FXS is characterized, in part, by hyperactivity, impaired behavioral flexibility, and the development of repetitive, or stereotyped, behaviors. While these phenotypes are influenced by striatal activity, few studies have examined FXS or FMRP in the context of striatal function. Here, we report enhanced repetitive behaviors in Fmr1 knockout (KO) compared to wild type (WT) mice according to multiple measures, including quantity and intensity of stereotypic behaviors in an open field and nose poking activity in an unbaited hole board test. However, using a baited version of the hole board assay, we see that KO mice do show some behavioral flexibility in that they make changes in their nose poking behavior following familiarization with an appetitive bait. By contrast, repeated exposure to cocaine (15mg/kg) promotes repetitive behavior in both WT and KO mice, in a manner mostly independent of genotype. Branch length alterations in medium spiny neurons (MSNs) of the dorsolateral striatum (DLS) are similar between WT cocaine-treated and KO saline-treated mice, possibly suggesting shared synaptic mechanisms. Overall, we suggest that scoring open field behavior is a sensitive measure for repetitive sensory-motor behaviors in Fmr1 KO mice. In addition, our findings show that synaptic contacts onto MSNs in the DLS should be examined in conjunction with measures of stereotypical behavior.

published proceedings

  • Brain Res

altmetric score

  • 1.5

author list (cited authors)

  • Huebschman, J. L., Monterrey, C. A., Foster, D. M., Omoregie, C. C., Cakir, A. E., Sevilla-Gutierrez, A., ... Smith, L. N.

citation count

  • 2

complete list of authors

  • Huebschman, Jessica L||Monterrey, Carolina A||Foster, Dorothy M||Omoregie, Chris C||Cakir, Alp E||Sevilla-Gutierrez, Adrian||Chow, Elsbeth C||Essoh, Amanda||Guo, Yuhong||Smith, Laura N

publication date

  • November 2022