Social experience in adolescence shapes prefrontal cortex structure and function in adulthood.

Area of Science:

• Neuroscience
• Developmental Biology
• Behavioral Science

Background:

• Adolescence is a critical period for prefrontal cortex (PFC) development.
• Social environment significantly impacts PFC maturation and can influence psychopathology.
• Disruptions during this period may have long-lasting neurobehavioral consequences.

Purpose of the Study:

• To investigate the long-term neurobehavioral effects of adolescent isolation in mice.
• To identify the underlying neural mechanisms in the ventromedial PFC (vmPFC).
• To explore the role of cytoskeletal regulatory pathways in these long-term changes.

Main Methods:

• Mice were subjected to social isolation during adolescence.
• Neurobehavioral assessments were conducted to evaluate habit formation, goal-directed behavior, and anhedonia.
• Electrophysiological recordings and molecular analyses were performed on the vmPFC.
• Interventions targeting cytoskeletal pathways were employed.

Main Results:

• Adolescent isolation induced persistent habit-like behaviors and anhedonia-like deficits.
• These behavioral changes were associated with dendritic spine over-abundance and hyper-excitability in the vmPFC.
• vmPFC hyperactivity was both necessary and sufficient for isolation-induced behavioral inflexibility.
• Isolation activated specific cytoskeletal pathways, and their repression prevented long-term neurobiological changes.

Conclusions:

• Adolescence represents a critical period for social influence on PFC maturation.
• Social isolation during adolescence can establish long-lasting neurobiological alterations in the vmPFC.
• These alterations contribute to behavioral inflexibility and reward deficits, potentially priming for psychopathology.
• Targeting specific molecular pathways may offer therapeutic avenues for mitigating the effects of early-life adversity.