Early-life stress impairs recognition memory and perturbs the functional maturation of prefrontal-hippocampal-perirhinal networks

Early life exposure to stressful situations impairs cognitive performance of adults and contributes to the etiology of several psychiatric disorders. Most of affected cognitive abilities rely on coupling by synchrony within complex neuronal networks, including prefrontal cortex (PFC), hippocampus (HP), and perirhinal cortex (PRH). Yet it remains poorly understood how early life stress (ELS) induces dysfunction within these networks during the course of development. Here we used intermittent maternal separation during the first 2 postnatal weeks to mimic ELS and monitored the recognition memory and functional coupling within prefrontal-hippocampal-perirhinal circuits in juvenile rats. While maternally-separated female rats showed largely normal behavior, male rats experiencing this form of ELS had poorer location and recency recognition memory. Simultaneous multi-site extracellular recordings of network oscillations and neuronal spiking from PFC, HP, and PRH in vivo revealed corresponding decrease of oscillatory activity in theta and beta frequency bands in the PFC of male but not female rats experiencing maternal separation. This deficit was accompanied by weaker cross-frequency coupling within juvenile prefrontal-hippocampal networks. These results indicate that already at juvenile age ELS mimicked by maternal separation induces sex-specific deficits in recognition memory that might have as underlying mechanism a disturbed communication between PFC and HP.