The Development of Prefrontal Cortex: The Maturation of Neurotransmitter Systems and Their Interactions

Abstract

This chapter provides an overview of the development of the prefrontal cortex that begins with the differentiation of its intrinsic projection and local circuit neurons during embryogenesis, but extends well beyond. Despite the early appearance of laminar patterns that reflect those seen in the adult brain, the architecture of synaptic connections and the maturation of intrinsic and extrinsic neurotransmitter systems continue to change in the prefrontal cortex during the postnatal period. It is particularly noteworthy that a variety of studies have demonstrated that the monoaminergic neurons, especially those employing dopamine as a neuromodulator, continue to infiltrate the cortical mantle until the early adult period. More recent evidence, however, even suggests that dopaminergic and serotonergic fibers form appositions with the same projection and local circuit neurons of the prefrontal cortex. Because of this convergence, a disturbance in the development of serotonergic projections in this region is associated with an increase of its dopaminergic innervation. Taken together, these findings suggest that these two monoaminergic systems may compete with each other for the establishment of functional territory on intrinsic neurons of the cortex, although it is not clear whether this interaction is mediated within the cortex itself or possibly at midbrain levels where the respective nuclei are located. Overall, the results described in this chapter suggest that the ontogenesis of the prefrontal cortex is a protracted process in which a marked degree of plasticity, even in the early stages of adulthood, contributes to the establishment of mature patterns of connectivity.