Early life stress leads to an aberrant spread of neuronal avalanches in the prefrontal-amygdala network in males but not females

Abstract Development of the brain networks is highly vulnerable to stressful events. Early life stress (ELS) has been linked to multifaceted cognitive and emotional deficits in adulthood. Despite a growing body of evidence showing ELS-induced structural and functional changes in the prefrontal cortex (PFC) and basolateral amygdala (BLA), a circuit crucial for emotional processing, our knowledge of the resulting changes in the network dynamics is incomplete. Here, we investigate how maternal separation (MS) affects prefrontal-amygdala network in terms of neuronal avalanches, spatiotemporal clusters of activity, using simultaneous multielectrode recordings in the medial PFC (mPFC) and the BLA of urethane-anaesthetized juvenile (postnatal day (p) 14 – p15) and young adult (p50 – p 60) rats. Firstly, we show that MS leads to an intensified spread of activity within both regions as reflected in the higher mean branching ratios of the avalanches. Next, we demonstrate that most of the avalanches occur locally in one region, however, a small percentage of avalanches has clusters of activity in both regions simultaneously. We show that in MS animals prefrontal clusters followed by activity in the amygdala tend to be larger compared to controls and each event in the mPFC is followed by smaller number of events in the BLA, pointing towards impaired spread of activity from the mPFC to the BLA. Interestingly, avalanche spread from the BLA to the mPFC remains unaffected by MS. Abovementioned effects manifest only in adulthood and, intriguingly, only in males highlighting prolonged developmental and sex-dependent nature of ELS outcome. Significance statement Brain criticality implies that the brain self-organizers towards critical state, characterized by sustained activity propagation reflected in the unitary branching ratios of neuronal avalanches. Here we show how adverse events during early periods of network maturation, namely ELS, can disrupt developmental trajectories of the critical dynamics in the mPFC-BLA circuit in a sex-specific manner. This study broadens our understanding of the critical dynamics emergence in the prefrontal-limbic network and highlights ELS as a potential criticality control parameter.