%0 Journal Article
%T Sex-Dependent Alterations in Social Behaviour and Cortical Synaptic Activity Coincide at Different Ages in a Model of Alzheimer¡¯s Disease
%A Cyril Bories
%A Matthieu J. Guitton
%A Carl Julien
%A Cyntia Tremblay
%A Mil¨¨ne Vandal
%A Meriem Msaid
%A Yves De Koninck
%A Fr¨¦d¨¦ric Calon
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0046111
%X Besides memory deficits, Alzheimer¡¯s disease (AD) patients suffer from neuropsychiatric symptoms, including alterations in social interactions, which are subject of a growing number of investigations in transgenic models of AD. Yet the biological mechanisms underlying these behavioural alterations are poorly understood. Here, a social interaction paradigm was used to assess social dysfunction in the triple-transgenic mouse model of AD (3xTg-AD). We observed that transgenic mice displayed dimorphic behavioural abnormalities at different ages. Social disinhibition was observed in 18 months old 3xTg-AD males compared to age and sex-matched control mice. In 3xTg-AD females, social disinhibition was present at 12 months followed by reduced social interactions at 18 months. These dimorphic behavioural alterations were not associated with alterations in AD neuropathological markers such as A¦Â or tau levels in the frontal cortex. However, patch-clamp recordings revealed that enhanced social interactions coincided temporally with an increase in both excitatory and inhibitory basal synaptic inputs to layer 2¨C3 pyramidal neurons in the prefrontal cortex. These findings uncover a novel pattern of occurrence of psychiatric-like symptoms between sexes in an AD model. Our results also reveal that functional alterations in synapse activity appear as a potentially significant substrate underlying behavioural correlates of AD.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0046111