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

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 have 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 describes the brain’s ability to maintain a balanced state in which neural activity spreads efficiently without becoming too weak or overly chaotic. This balance can be measured through neuronal avalanches, bursts of cascading activity across interconnected neurons. Here, we show that early life stress (ELS) — adverse experiences during early brain development — disrupts the development of avalanche patterns in the connection between the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA), brain regions involved in emotion and stress regulation. These effects were detected in males but not females. Our findings improve understanding of how stable brain activity develops in emotional brain networks and suggest that early life stress is an important factor influencing this critical balance.