Mature parvalbumin interneuron function in prefrontal cortex requires activity during a postnatal sensitive period.

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Cognitive Neuroscience

Background:

• Hubel and Wiesel identified critical periods for visual cortex development.
• The existence of similar sensitive periods in non-sensory cortices like the prefrontal cortex is under investigation.
• Prefrontal cortex (PFC) development is crucial for cognitive functions and behavioral flexibility.

Purpose of the Study:

• To investigate whether a sensitive period exists for prefrontal cortex maturation.
• To determine the long-term effects of inhibiting prefrontal parvalbumin (PV)-expressing interneurons during development.
• To explore the potential for reversing developmental impairments in adulthood.

Main Methods:

• Inhibition of prefrontal PV interneurons in mice during juvenile and adolescent stages.
• Assessment of adult prefrontal circuit connectivity and in vivo network function.
• Evaluation of behavioral flexibility in adult mice.
• Targeted activation of PV interneurons in adulthood to assess reversibility.

Main Results:

• Inhibition of PV interneurons during development led to persistent impairments in adult PFC connectivity, network function, and behavioral flexibility.
• Suppression of PV interneuron activity in adulthood had no lasting effects.
• Targeted activation of PV interneurons in adulthood successfully reversed the developmental impairments.

Conclusions:

• This study identifies an activity-dependent sensitive period for prefrontal cortex maturation.
• Abnormal PV interneuron activity during development significantly alters adult PFC function and cognitive behavior.
• Interventions targeting PV interneurons during adulthood can potentially reverse developmental deficits.