An altered cognitive strategy associated with reduction of synaptic inhibition in the prefrontal cortex after social play deprivation in rats

Experience-dependent organization of neuronal connectivity is a critical component of brain development, but how experience shapes prefrontal cortex (PFC) development is unknown. Here, we assessed how social play behaviour, which is highly abundant during post-weaning development, shapes PFC function and connectivity. We subjected juvenile rats to social play deprivation (SPD), followed by resocialization until adulthood. In a PFC-dependent probabilistic reversal learning task, SPD rats earned a similar number of rewards, but achieved more reversals than control rats. Computational trial-by-trial analysis showed that SPD rats displayed a simplified cognitive strategy. In addition, inhibitory synaptic currents were significantly reduced in layer 5 PFC cells of SPD rats, with specific changes in parvalbumin- and cannabinoid receptor 1-positive perisomatic inhibitory synapses. Thus, SPD has a long-lasting impact on PFC inhibition via synapse-specific alterations, associated with simplified cognitive strategies. We conclude that proper PFC development depends on pertinent social experience during a restricted time period.