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Published Online: 1 November 2000

Neural Networks: Neural Systems IV: Prefrontal Cortex

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 figure 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.
Figure
The schematic diagram on the left illustrates the synaptic connections of supragranular pyramidal neurons in the prefrontal cortex of the monkey. Pyramidal neurons in layers 2–3 of the monkey prefrontal cortex are clustered into stripe-like arrays (average dimensions: 275 μm by 1.8 mm) that are reciprocally connected by intrinsic axon collaterals. Intrinsic axon terminals from pyramidal neurons in one stripe form excitatory synapses on the dendritic spines (a) of pyramidal neurons (p) located in other intrinsic clusters. These pyramidal neurons in turn send intrinsic axon collaterals (b) to the first stripe. Intrinsic axon terminals from supragranular pyramidal neurons also form asymmetric synapses on dendritic shafts (c). Many of these dendritic shafts have the morphological characteristics of local circuit neurons and are hypothesized to include the wide-arbor (WA) class of γ-aminobutyric acid (GABA) cells. The size of the axon arbors of this class of GABA neurons suggests that they extend into the gap or interstripe region, where they may provide inhibitory input to the cell bodies of pyramidal neurons (d). Pyramidal neurons that furnish intrinsic axon collaterals also provide associational principal axon projections (e) to other areas of the prefrontal cortex. The axon terminals of these associational principal axon projections form excitatory synapses with the dendritic spines of other pyramidal neurons (f). Note that the branching axons and axon terminals of intrinsic stripes are confined to layers 1–3, whereas those of the associational stripes span all six cortical layers. On the right, the cluster of labeled intrinsic axon terminals arises from an injection site in the prefrontal cortex located approximately 6 mm medial to (left of) the cluster. Note that the dense array of labeled axons and boutons is confined to layers 1–3 and that this cluster is associated with horizontally oriented axons that travel through the gray matter (see arrows).

Footnote

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.

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Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 1752
PubMed: 11058467

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Published online: 1 November 2000
Published in print: November 2000

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David A. Lewis, M.D.
Pittsburgh, Pa.

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