Format

Send to

Choose Destination
See comment in PubMed Commons below
Front Behav Neurosci. 2013 Nov 21;7:172. doi: 10.3389/fnbeh.2013.00172. eCollection 2013.

Hyperactivity, perseveration and increased responding during attentional rule acquisition in the Fragile X mouse model.

Author information

1
Department of Integrative Neurophysiology, Centre for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands ; Sylics (Synaptologics BV) Amsterdam, Netherlands.

Abstract

Attentional deficits and executive function impairments are common to many neurodevelopmental disorders of intellectual disability and autism, including Fragile X syndrome (FXS). In the knockout mouse model for FXS, significant changes in synaptic plasticity and connectivity are found in the prefrontal cortex (PFC)-a prominent region for attentional processing and executive control. Given these alterations in PFC synaptic function, we tested whether adult Fragile X knockout mice exhibited corresponding impairments in inhibitory control, perseveration, and sustained attention. Furthermore, we investigated individual performance during attentional rule acquisition. Using the 5-choice serial reaction time task, our results show no impairments in inhibitory control and sustained attention. Fragile X knockout mice exhibited enhanced levels of correct and incorrect responding, as well as perseveration of responding during initial phases of rule acquisition, that normalized with training. For both knockout and wild type mice, pharmacological attenuation of metabotropic glutamate receptor 5 signaling did not affect response accuracy but reduced impulsive responses and increased omission errors. Upon rule reversal, Fragile X knockout mice made more correct and incorrect responses, similar to the initial phases of rule acquisition. Analogous to heightened activity upon novel rule acquisition, Fragile X knockout mice were transiently hyperactive in both a novel open field (OF) arena and novel home cage. Hyperactivity ceased with familiarization to the environment. Our findings demonstrate normal inhibitory control and sustained attention but heightened perseveration, responding, and hyperactivity during novel rule acquisition and during exposure to novel environments in Fragile X knockout mice. We therefore provide evidence for subtle but significant differences in the processing of novel stimuli in the mouse model for the FXS.

KEYWORDS:

5-choice serial reaction time task; Fragile X; MPEP; attention; hyperactivity; learning; perseveration; prefrontal cortex

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Frontiers Media SA Icon for PubMed Central
    Loading ...
    Support Center