Parallel learning and cognitive flexibility impairments between Fmr1 knockout mice and individuals with fragile X syndrome.
Parallel learning and cognitive flexibility impairments between Fmr1 knockout mice and individuals with fragile X syndrome.
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DOI：
10.3389/fnbeh.2022.1074682
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发表时间：
2022
影响因子：
3
通讯作者：
中科院分区：
文献类型：
--
作者：
Fragile X Syndrome (FXS) is a monogenic condition that leads to intellectual disability along with behavioral and learning difficulties. Among behavioral and learning difficulties, cognitive flexibility impairments are among the most commonly reported in FXS, which significantly impacts daily living. Despite the extensive use of the Fmr1 knockout (KO) mouse to understand molecular, synaptic and behavioral alterations related to FXS, there has been limited development of translational paradigms to understand cognitive flexibility that can be employed in both animal models and individuals with FXS to facilitate treatment development. To begin addressing this limitation, a parallel set of studies were carried out that investigated probabilistic reversal learning along with other behavioral and cognitive tests in individuals with FXS and Fmr1 KO mice. Fifty-five adolescents and adults with FXS (67% male) and 34 age- and sex-matched typically developing controls (62% male) completed an initial probabilistic learning training task and a probabilistic reversal learning task. In males with FXS, both initial probabilistic learning and reversal learning deficits were found. However, in females with FXS, we only observed reversal learning deficits. Reversal learning deficits related to more severe psychiatric features in females with FXS, whereas increased sensitivity to negative feedback (lose:shift errors) unexpectedly appear to be adaptive in males with FXS. Male Fmr1 KO mice exhibited both an initial probabilistic learning and reversal learning deficit compared to that of wildtype (WT) mice. Female Fmr1 KO mice were selectively impaired on probabilistic reversal learning. In a prepotent response inhibition test, both male and female Fmr1 KO mice were impaired in learning to choose a non-preferred spatial location to receive a food reward compared to that of WT mice. Neither male nor female Fmr1 KO mice exhibited a change in anxiety compared to that of WT mice. Together, our findings demonstrate strikingly similar sex-dependent learning disturbances across individuals with FXS and Fmr1 KO mice. This suggests the promise of using analogous paradigms of cognitive flexibility across species that may speed treatment development to improve lives of individuals with FXS.
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影响因子：
4.7
作者：
Amodeo, Dionisio A.;Cuevas, Laura;Ragozzino, Michael E.
通讯作者：
Ragozzino, Michael E.
影响因子：
6.8
作者：
D'Cruz AM;Mosconi MW;Ragozzino ME;Cook EH;Sweeney JA
通讯作者：
Sweeney JA
影响因子：
3.9
作者：
Schmitt LM;Sweeney JA;Erickson CA;Shaffer R
通讯作者：
Shaffer R
影响因子：
3.6
作者：
Stelzel, Christine;Fiebach, Christian J.;Cools, Roshan;Tafazoli, Sharwin;D'Esposito, Mark
通讯作者：
D'Esposito, Mark
影响因子：
2.4
作者：
D'Cruz, Anna-Maria;Ragozzino, Michael E.;Mosconi, Matthew W.;Shrestha, Sunil;Cook, Edwin H.;Sweeney, John A.
通讯作者：
Sweeney, John A.