DISTURBED PREFRONTAL NETWORK ORGANIZATION COULD CONTRIBUTE TO POST-WEANING SOCIAL ISOLATION-INDUCED ABNORMAL SOCIAL BEHAVIOUR
01/30/2020
Christina Miskolczi1, Laszlo Biro1, Biborka Bruzsik1, Huba Szebik1, David Lorincz1, Zoltan Kristof Varga1, Laszlo Szente1, Orsolya Horvath1, Jozsef Halasz1, Mate Toth1, Eva Mikics1
1 Department of Behavioural Neurobiology, Institute of Experimental Medicine
Brain regions regulating social behaviour undergo dynamic changes in early life, rendering them vulnerable to social adversities experienced during this period. Here we aimed to characterize social behavioural changes induced by post-weaning social isolation (modelling childhood neglect) in mice and investigate underlying network disturbances in the prefrontal cortex(PFC), a principal modulator of social behaviour. Mice were weaned at P21 and housed either socially (4 mice/cage) or were isolated (alone) until adulthood. In adulthood, we used the social interaction and resident-intruder(RI) tests to investigate social behaviour and aggression. Using immunohistochemistry and confocal imaging, we investigated (1)c-Fos activation and co-activation patterns of PFC subregions, (2)the proportion of parvalbumin-containing(PV+) and perineuronal net-positive(PNN+) neurons in each subregion and (3)the activation(c-Fos+) of these cell populations under resting conditions and following social encounter(RI). Isolated mice display social disturbances in adulthood, manifested as increased defensive and abnormal aggressive behavior disregarding species-specific rules. Correlation matrices reveal that social encounter exerts differential c-Fos activation patterns in the PFC of isolated animals. In dorsal PFC regions RI increased the activity of PV+PNN+ neurons in both social and isolated animals. Conversely, in the infralimbic cortex social encounter decreased the activity of PV+PNN+ neurons in socially-reared mice, an effect absent in isolated animals. In conclusion, social isolation leads to social behavioural abnormalities and impaired PV+PNN+ activity following social encounter. Our results contribute to understanding how disruption of neuronal network organization during development could lead to social abnormalities in adulthood.