NARP-RELATED ALTERATIONS IN THE EXCITATORY AND INHIBITORY CIRCUITRY OF SOCIALLY ISOLATED MICE: DEVELOPMENTAL INSIGHTS AND IMPLICATIONS FOR AUTISM SPECTRUM DISORDER

Background: Social isolation during a critical period of postnatal development causes persistent alterations in behaviors and cortical neural circuits. Here, we examined the acute and long-term effects of juvenile social isolation during a critical period on the intrinsic firing properties of prefrontal cortex (PFC) pyramidal neurons, the expression of neuronal activity–regulated pentraxin (NARP) and parvalbumin (PV) in the PFC, and social behavioral outcomes. We further investigated the translational relevance of NARP expression in human autism spectrum disorder (ASD).
Methods: Mice were subjected to social isolation throughout the postnatal critical period from postnatal day 21 to 35 (P21–P35) and compared with age-matched group-housed controls. Electrophysiological recordings of PFC pyramidal neurons and analysis of NARP and PV expression were conducted at P35. Social behavior was assessed in adulthood using a three-chamber setting. In parallel, NARP expression was quantified in lymphoblastoid cell lines derived from adolescents with ASD and typically developing (TD) individuals.
Results: Social isolation during the postnatal critical period induced significant reduction in the firing properties of PFC pyramidal neurons at P35, accompanied by changes in NARP expression. In adulthood, mice exposed to critical period social isolation displayed impaired social recognition, while exhibiting preserved levels of overall social preference. Moreover, NARP expression was significantly decreased in lymphoblastoid cell lines from adolescents with ASD relative to TD controls.
Conclusion: Our study highlights the role of electrophysiological properties, as well as NARP and PV expression in the PFC in mediating the developmental consequences of social isolation on behavior.