Prefrontal cortical-specific differences in behavior and synaptic plasticity between adolescent and adult mice

Area of Science:

• Neuroscience
• Developmental Biology
• Cognitive Science

Background:

• Adolescence is a critical period for neuropsychological disorders, marked by reduced cognitive control and increased risk-taking.
• The prefrontal cortex (PFC) is crucial for regulating impulsive behavior, but its developmental trajectory and functional maturation are not fully understood.
• Understanding PFC development is key to explaining adolescent behavioral changes and vulnerability to disorders.

Purpose of the Study:

• To investigate the developmental changes in prefrontal cortex (PFC)-mediated cognitive functions from adolescence to adulthood.
• To compare the functional maturation of the PFC with other cortical areas during this period.
• To identify the underlying cellular mechanisms, specifically synaptic plasticity, responsible for cognitive differences between adolescent and adult mice.

Main Methods:

• Cognitive behavioral tasks were administered to adolescent and adult mice.
• Synaptic plasticity, specifically long-term potentiation (LTP), was measured in the PFC and barrel cortex.
• Intrinsic neuronal excitability and N-methyl-d-aspartate (NMDA) receptor subunit expression were analyzed in PFC neurons.

Main Results:

• Adolescent mice performed poorly on PFC-dependent tasks but similarly on non-PFC-dependent tasks compared to adults.
• A significant decrease in LTP was observed in the upper layers of the adolescent PFC, but not in the barrel cortex.
• Reduced NR2A NMDA receptor subunit expression was found in the adult PFC, correlating with increased LTP, while GABAergic signaling and intrinsic excitability remained unchanged.

Conclusions:

• Adolescence is characterized by PFC-specific physiological and behavioral changes, including reduced synaptic plasticity.
• Impaired cognitive control in adolescents may stem from decreased LTP in the PFC, linked to lower NR2A NMDA receptor expression.
• These findings highlight the unique developmental trajectory of the PFC and its role in adolescent behavior.