Social Play Behavior Is Critical for the Development of Prefrontal Inhibitory Synapses and Cognitive Flexibility in Rats

Abstract

Sensory driven activity during early life is critical for setting up the proper connectivity of the sensory cortices. We ask here whether social play behavior, a particular form of social interaction that is highly abundant during postweaning development, is equally important for setting up connections in the developing prefrontal cortex (PFC). Young male rats were deprived from social play with peers during the period in life when social play behavior normally peaks [postnatal day 21–42] (SPD rats), followed by resocialization until adulthood. We recorded synaptic currents in layer 5 cells in slices from medial PFC of adult SPD and control rats and observed that inhibitory synaptic currents were reduced in SPD slices, while excitatory synaptic currents were unaffected. This was associated with a decrease in perisomatic inhibitory synapses from parvalbumin-positive GABAergic cells. In parallel experiments, adult SPD rats achieved more reversals in a probabilistic reversal learning (PRL) task, which depends on the integrity of the PFC, by using a more simplified cognitive strategy than controls. Interestingly, we observed that one daily hour of play during SPD partially rescued the behavioral performance in the PRL, but did not prevent the decrease in PFC inhibitory synaptic inputs. Our data demonstrate the importance of unrestricted social play for the development of inhibitory synapses in the PFC and cognitive skills in adulthood and show that specific synaptic alterations in the PFC can result in a complex behavioral outcome.SIGNIFICANCE STATEMENTThis study addressed the question whether social play behavior in juvenile rats contributes to functional development of the prefrontal cortex (PFC). We found that rats that had been deprived from juvenile social play (social play deprivation - SPD) showed a reduction in inhibitory synapses in the PFC and a simplified strategy to solve a complex behavioral task in adulthood. Providing one daily hour of play during SPD partially rescued the cognitive skills in these rats, but did not prevent the reduction in PFC inhibitory synapses. Our results demonstrate a key role for unrestricted juvenile social play in PFC development and emphasize the complex relation between PFC circuit connectivity and cognitive function.

Social play behavior shapes the development of prefrontal inhibition in a region-specific manner

“…1E and 1J), which suggests that the increase in inhibitory currents reflects the formation of new inhibitory synapses during this period as well as an increase in activity-dependent release. Consistent with our previous findings (Bijlsma et al, 2022), mIPSC frequency was reduced in the mPFC of SPD slices at P85, but the reduction was less pronounced at P42 (Fig. 1I).…”

“…It is therefore likely that a synaptic change in one of the regions will affect the circuit development in the other. Consistent with our previous findings (Bijlsma et al, 2022), we observed that SPD affects the inhibitory, but not the excitatory, connections in both PFC regions. SPD resulted in reduced synaptic inhibition, reminiscent of the impaired development of inhibitory connections that has been described after sensory deprivation (Mowery et al, 2019;Reh et al, 2020).…”

Perinatal Opioid Exposure Leads to Decreased Social Play in Adolescent Male and Female Rats: Potential Role of Oxytocin Signaling in Brain Regions Associated with Social Reward

“…Opioids, particularly μ- and κ-receptor agonists, generally inhibit OT and vasopressin (AVP) neuronal firing, thereby suppressing peptide release (Douglas and Russell, 2001; Inenaga et al, 1990; Li et al, 2001; Lutz-Bucher and Koch, 1980; Van de Heijning et al, 1991), likely via presynaptic mechanisms (Clarke and Wright, 1984; Zhao et al, 1988). Interestingly, juvenile play also facilitates the development of inhibitory prefrontal cortex synapses necessary for cognitive and executive function (Bijlsma et al, 2022). This suggests that clinical reports of reduced social behavior and deficits in cognitive performance may be inter-related (Yeoh et al, 2019).…”

Opportunities for risk-taking during play alters cognitive performance and prefrontal inhibitory signalling in rats of both sexes

“…working memory, impulse control, attention, planning and decision making), has been observed in play-deprived animals. Indeed, we have recently demonstrated that deprivation of social play affects the synaptic connectivity in the medial prefrontal cortex (mPFC) of adult rats; we found a reduction in specific inhibitory synaptic inputs onto layer 5 pyramidal cells (Bijlsma et al, 2022, 2023). These findings support the notion that social play behaviour subserves the development of emotional and cognitive capacities and their PFC substrate.…”