Parallel learning and cognitive flexibility impairments between Fmr1 knockout mice and individuals with fragile X syndrome
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...
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Published in | Frontiers in behavioral neuroscience Vol. 16; p. 1074682 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Research Foundation
05.01.2023
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | 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
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
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
KO mice exhibited both an initial probabilistic learning and reversal learning deficit compared to that of wildtype (WT) mice. Female
KO mice were selectively impaired on probabilistic reversal learning. In a prepotent response inhibition test, both male and female
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
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
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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was submitted to Pathological Conditions, a section of the journal Frontiers in Behavioral Neuroscience These authors have contributed equally to this work and share first authorship Edited by: Martine Ammassari-Teule, National Research Council (CNR), Italy Reviewed by: Leonardo Restivo, Université de Lausanne, Switzerland; Maria Vincenza Catania, Institute of Neurological Sciences (CNR), Italy |
ISSN: | 1662-5153 1662-5153 |
DOI: | 10.3389/fnbeh.2022.1074682 |