Adolescent Parvalbumin Expression in the Left Orbitofrontal Cortex Shapes Sociability in Female Mice.

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Social Neuroscience

Background:

• Adolescent social experiences are crucial for prefrontal cortex maturation in mammals.
• The specific cortical circuits and sex-specific mechanisms by which social experience shapes adult social behavior remain unclear.

Purpose of the Study:

• To investigate the impact of postweaning social isolation (PWSI) on social behaviors in male and female mice.
• To identify the neural circuits in the orbitofrontal cortex (OFC) involved in sex-specific social behavior changes.

Main Methods:

• Examined social-approaching behaviors in male and female mice subjected to PWSI.
• Measured parvalbumin (PV) expression and neural activity in the left orbitofrontal cortex (OFC_L).
• Utilized CRISPR/Cas9 and optogenetics to manipulate PV expression and neuronal activity in the OFC_L.

Main Results:

• PWSI induced hypersociability and reduced PV expression specifically in female mice.
• PWSI decreased the number and activity of neurons in the female OFC_L during social sniffing.
• PV knockdown in the female OFC_L mimicked the effects of social isolation, enhancing sociability and reducing social sniffing-evoked activity.

Conclusions:

• Adolescent social experience is essential for the maturation of PV⁺ inhibitory circuits in the OFC_L.
• Maturation of these circuits is critical for shaping female social behavior by regulating OFC_L activity.
• Disruptions in adolescent social experience can lead to sex-specific alterations in social behavior via OFC_L circuit dysfunction.