Cell adhesion presence during adolescence controls the architecture of projection-defined prefrontal cortical neurons and reward-related action strategies later in life

Summary

During teenage years, the brain undergoes important structural changes that set the stage for adult decision-making abilities. This study found that a cell adhesion protein called β1-integrin plays a critical role during adolescence in stabilizing connections between brain cells in the prefrontal cortex. When this protein was missing during the teenage years, adult mice struggled to make good decisions about rewards and could not adjust their behavior when circumstances changed. The research suggests that proper brain development during adolescence requires these cellular adhesion molecules to build the neural circuits needed for intelligent decision-making later in life.

Background

Adolescent brain development involves significant neuronal remodeling in the prefrontal cortex, but relationships between this remodeling and behavior are largely undefined. Integrins are cell adhesion factors linking the extracellular matrix to intracellular actin cytoskeleton. Previous studies suggest β1-integrins may stabilize dendrites and synapses during adolescence.

Objective

To determine whether β1-integrin presence in the prelimbic prefrontal cortex during adolescence is necessary for adaptive action selection in adulthood, and to characterize the dendritic architecture of projection-defined prefrontal neurons receiving input from the basolateral amygdala and projecting to the dorsomedial striatum.

Results

β1-integrin presence during adolescence, but not adulthood, was necessary for mice to select actions based on reward likelihood and value. Loss of β1-integrins during adolescence triggered overexpression of immature stubby-type dendritic spines at the expense of mature mushroom-shaped spines on projection-defined neurons. Projection-defined neurons exhibited more adult-like morphology compared to general layer V populations.

Conclusion

β1-integrin-mediated cell adhesion during adolescence stabilizes dendritic spines on prefrontal neurons within a basolateral amygdala-prelimbic-dorsomedial striatum circuit, providing structural substrates necessary for adaptive decision-making in adulthood. This work implicates cell adhesion molecules as crucial factors in adolescent brain development and potential therapeutic targets for neurodevelopmental disorders.
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