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

Abstract

Adolescent brain development is characterized by neuronal remodeling in the prefrontal cortex; relationships with behavior are largely undefined. Integrins are cell adhesion factors that link the extracellular matrix with intracellular actin cytoskeleton. We find that β1-integrin presence in the prelimbic prefrontal cortex (PL) during adolescence, but not adulthood, is necessary for mice to select actions based on reward likelihood and value. As such, adult mice that lacked β1-integrin during adolescence failed to modify response strategies when rewards lost value or failed to be delivered. This pattern suggests that β1-integrin-mediated neuronal development is necessary for PL function in adulthood. We next visualized adolescent PL neurons, including those receiving input from the basolateral amygdala (BLA) – thought to signal salience – and projecting to the dorsomedial striatum (DMS) – the striatal output by which the PL controls goal-seeking behavior. Firstly, we found that these projection-defined neurons had a distinct morphology relative to general layer V PL neurons. Secondly, β1-integrin loss triggered the overexpression of stubby-type dendritic spines at the expense of mature spines, including on projection-defined neurons. This phenotype was not observed when β1-integrins were silenced before or after adolescence. Altogether, our experiments localize β1-integrin-mediated cell adhesion within a developing di-synaptic circuit coordinating adaptive action