Cellular activation in limbic brain systems during social play behaviour in rats

Abstract

Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer-peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited. Therefore, the purpose of this study was to map the neural circuits involved in social play behaviour in rats. This was achieved by examining cellular activity after social play using the immediate early gene c-fos as a marker. After a session of social play behaviour, pronounced increases in c-fos expression were observed in the medial prefrontal cortex, medial and ventral orbitofrontal cortex, dorsal striatum, nucleus accumbens core and shell, lateral amygdala, several thalamic nuclei, dorsal raphe and the pedunculopontine tegmental nucleus. Importantly, the cellular activity patterns after social play were topographically organised in this network, as indicated by play-specific correlations in c-fos activity between regions with known direct connections. These correlations suggest involvement in social play behaviour of the projections from the medial prefrontal cortex to the striatum, and of amygdala and monoaminergic inputs to frontal cortex and striatum. The analyses presented here outline a topographically organised neural network implicated in processes such as reward, motivation and cognitive control over behaviour, which mediates social play behaviour in rats.

Dopaminergic Neurotransmission in the Nucleus Accumbens Modulates Social Play Behavior in Rats

“…Our previous functional anatomical and pharmacological inactivation studies (van Kerkhof et al, 2013(van Kerkhof et al, , 2014 suggested that these subregions are differentially involved in social play behavior. However, with regard to the modulation of social play by local opioid and cannabinoid signaling, there does not seem to be a major difference between the NAc core and shell (Trezza et al, 2011(Trezza et al, , 2012.…”

“…Previous studies have shown that the nucleus accumbens (NAc), a brain region widely implicated in reward and motivation (Berridge and Kringelbach, 2008;Everitt and Robbins, 2005;Floresco, 2015), modulates the positive subjective properties of social play behavior in rats (Gordon et al, 2002;Trezza et al, 2011Trezza et al, , 2012van Kerkhof et al, 2013van Kerkhof et al, , 2014Vanderschuren et al, 1995b). Interestingly, peer-peer interactions in 4-week-old rats increase dopamine activity in the NAc (Robinson et al, 2011).…”

Social Play Behavior in Adolescent Rats is Mediated by Functional Activity in Medial Prefrontal Cortex and Striatum

“…Using c-fos as an activity marker, enhanced neuronal activity has been observed after social play behavior in several medial PFC regions, ie, anterior cingulate, prelimbic cortex (PrL) and infralimbic cortex (IL), as well as in orbitofrontal cortex (OFC) regions (Cheng et al, 2008;Gordon et al, 2002;Van Kerkhof et al, 2013). In keeping with these findings, the structure of social play and its sensitivity to social cues was found to be altered after neonatal lesions of the PFC or OFC (Bell et al, 2009;Panksepp et al, 1994;Pellis et al, 2006;Schneider and Koch, 2005).…”

“…Interestingly, this somewhat resembles the effect of neonatal lesions of the medial PFC (Bell et al, 2009), suggesting involvement of projections from medial PFC to striatum in social play behavior. Further evidence for an involvement of corticostriatal projections is provided by immediate early gene expression studies, demonstrating that social play behavior induces c-fos expression in the striatum (Cheng et al, 2008;Gordon et al, 2002;Van Kerkhof et al, 2013). Interestingly, the levels of c-fos induced in medial PFC regions were found to correlate with the levels of c-fos in their striatal projection areas, suggesting that these projections are involved in social play behavior (Van Kerkhof et al, 2013).…”

“…However, most of these studies used either indirect approaches (Cheng et al, 2008;Gordon et al, 2002;Van Kerkhof et al, 2013) or neonatal lesions (Bell et al, 2009;Panksepp et al, 1994;Pellis et al, 1993Pellis et al, , 2006Schneider and Koch, 2005), which may disrupt normal brain development and/or lead to compensatory changes in non-affected structures. Therefore, here we investigated the role of PFC and striatum subregions in social play behavior using a temporary pharmacological inactivation technique, which allows for transient disruption of functional activity but leaves normal brain development and function intact (Martin, 1991;McFarland and Kalivas, 2001;Van Duuren et al, 2007).…”