Different cerebral regions in the human brain have specific patterns of local neuronal circuitry and structure that are designed to carry out the distinct functions of the region. The prefrontal cortex is involved in mediating aspects of cognition, particularly tasks that involve working memory or the temporal integration of information. This kind of information processing depends not only on long-range connections between the prefrontal cortex and other cortical areas, but also on local axon collaterals linking neighboring noncontiguous cell groups in the prefrontal cortex with each other. The F1 depicts a basic functional unit of prefrontal cortex circuitry that could serve as the anatomic substrate for the types of dynamic neuronal interactions that occur in relation to the behavioral events subserved by the prefrontal cortex. The intrinsic axon collaterals of pyramidal neurons in layers 2 and 3 of the prefrontal cortex, which travel horizontally through the cortical gray matter, exhibit divergence, convergence, and reciprocity of connections across discrete prefrontal cortex cell groups. The divergence of axon collaterals permits a spatially restricted input to recruit an array of neurons whose coordinated activity is required to generate a particular response. The convergence of axon collaterals enables multiple discontinuous points across the cortical surface to provide input to a single point. This arrangement allows divergent neuronal inputs to be relayed to the same location, facilitating the integration of their information content for a specific task. The reciprocity of axonal connections provides for bidirectional influences among different groups of neurons. The presence of reciprocal excitatory connections among spatially segregated locations in prefrontal cortical neuronal sets may contribute to producing sustained neuronal activity of the kind that is seen during the performance of certain psychological tasks, like delayed response or working memory tasks. It is of interest that the interconnected groups of neurons in the prefrontal cortex appear to be larger than in other cortical association regions, perhaps reflecting the complexity of the psychological tasks that the prefrontal cortex subserves.

Address reprint requests to Dr. Tamminga, Maryland Psychiatric Research Center, University of Maryland, P.O. Box 21247, Baltimore, MD 21228. Image adapted with permission from Melchitzky DS, Sesack SR, Pucak ML, Lewis DH: Synaptic targets of pyramidal neurons providing intrinsic horizontal connections in monkey prefrontal cortex. J Comp Neurol 1998; 390:211–224, Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.