This study describes cytoarchitectonic criteria to define the prefrontal cortical areas in the mouse brain (C57BL/6 strain). Currently, well-illustrated mouse brain stereotaxic atlases are available, which, however, do not provide a description of the distinctive cytoarchitectonic characteristics of individual prefrontal areas. Such a description is of importance for stereological, neuronal tracing, and physiological, molecular and neuroimaging studies in which a precise parcellation of the prefrontal cortex (PFC) is required. The present study describes and illustrates: the medial prefrontal areas, i.e., the infralimbic, prelimbic, dorsal and ventral anterior cingulate and Fr2 area; areas of the lateral PFC, i.e., the dorsal agranular insular cortical areas and areas of the ventral PFC, i.e., the lateral, ventrolateral, ventral and medial orbital areas. Each cytoarchitectonically defined boundary is corroborated by one or more chemoarchitectonic stainings, i.e., acetylcholine esterase, SMI32, SMI311, dopamine, parvalbumin, calbindin and myelin staining.

Cytoarchitectonic characterization of borders is necessary for stereological studies (e.g., total cell number estimation), in which particular cortical areas have to be defined. In this study, cytoarchitectonic characteristics are described and illustrated for the rat ventral or orbital frontal cortical areas, i.e., the lateral-, ventrolateral-, ventral- and medial-orbital areas; and for the lateral frontal cortical areas, i.e., the agranular insular and the dorsolateral orbital cortical area. Each cytoarchitectonic-defined boundary is corroborated by one or more of the immunocytochemical stainings for dopaminergic fibers, SMI-32 positive neurons, calbindin and parvalbumin positive neurons. Each immunocytochemical staining, however, shows a characteristic subset of the cytoarchitectonical borders. The dorsal agranular insular area (AId) and the dorsolateral orbital area (DLO) have been subdivided into a dorsal and a ventral part based upon differences between these parts in the Nissl and immunocytochemical stainings. The posterior part of VLO has a different structure and is, therefore, indicated as VLOp (VLO, posterior part).

This study compares the cytoarchitectonic parcellation of the prefrontal cortex (PFC) in the mouse as presented in publications that are commonly used for identifying brain areas. Agreement was found to be greater for boundaries in the medial PFC than in the lateral PFC and lowest for those in the orbital areas of the PFC. In this review, we explain and illustrate in a selected series of photographs and stereotactic pictures the differences in location and terminology of the different prefrontal cortical areas. The significance of cytoarchitectonic parcellation is discussed.

Objectives Neuroimaging studies note lithium-related increases in the volume of gray matter in prefrontal cortex (PFC) and hippocampus. Postmortem human studies report alterations in neuronal and glial cell density and size in the PFC of lithium-treated subjects. Rodents treated with lithium exhibit cell proliferation in the dentate gyrus (DG) of the hippocampus. However, it is not known whether hippocampal and PFC volume are also increased in these animals or whether cell number in the PFC is altered. Methods Using stereological methods, this study estimated the total number of neurons, glia and the packing density of astrocytes in the DG and PFC of normal adult mice treated with lithium and evaluated the total volume of these regions and the entire neocortex. Results Lithium treatment increased the total number of neurons and glia in the DG (25% and 21%, respectively) and the density of astrocytes but did not alter the total number in the PFC. However, the volume of the hippocampus and its subfields, the PFC and its subareas, and the entire neocortex were not altered by lithium. Conclusions Both neuronal and glial cells accounted for lithium-induced cell proliferation in the DG. That the number of neurons and glia were unchanged in the PFC is consistent with the view that this region is not a neurogenic zone. Further studies are required to clarify the impact of lithium treatment on the PFC under pathological conditions and to investigate the dissociation between increased cell proliferation and unchanged volume in the hippocampus.