Figure 2.

Schematic illustrations to depict the MD-PFC afferents and synaptic pruning under both normal and abnormal developmental conditions. The arrow sizes represent the relative numbers/densities of MD-PFC afferent fibers; whereas the number of dendritic branches in the PFC pyramidal neurons reflect changes in synaptic density and dendritic complexity. During normal development, both thalamocortical afferent fibers and dendritic branches of pyramidal neurons in the PFC are underdeveloped in the early neonate, over-produced during the juvenile and adolescent periods, and then reduced to normal levels in adulthood by eliminating the excess presynaptic axonal arbors (thalamocortical fibers) and/or postsynaptic dendrites. In contrast, as speculated, decreases in MD activity could result in a loss of synaptic drive to the PFC early in development, leading to a decrease in synaptic density, as is observed in patients with schizophrenia. Conversely, a presumably overactive thalamocortical drive to the PFC, could lead to a failure of the normal developmental synaptic pruning, resulting in increased spine density or hyperconnectivity, as demonstrated in autism.