ReviewThe medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics
Introduction
The mammalian prefrontal cortex has been classically defined and delineated by anatomical criteria such as cytoarchitectonic features (granular vs. agranular characteristics) [15], connectivity with the mediodorsal thalamic nucleus [1], [6], [71], [73], [76], [105], [111], [161], [168], input of dopaminergic fibers from the ventral mesencephalon, or a combination of these criteria [7], [13], [48], [49], [196], [200], [211]. The rat prefrontal cortex is, in general, tentatively divided into three topologically different regions. First, a medially located cortical region, the medial prefrontal cortex, which constitutes the major portion of the medial wall of the hemisphere anterior and dorsal to the genu of the corpus callosum. Second, a ventrally located cortical region that is termed the orbital prefrontal cortex and that lies in part dorsal to the caudal end of the olfactory bulb in the dorsal bank of the rhinal sulcus. Third, a laterally located cortical region, the lateral or sulcal prefrontal cortex, which is also referred to as the agranular insular cortex and, in rats, is located in the anterior part of the rhinal sulcus [49], [76], [105], [111], [112], [172], [173], [183].
The medial prefrontal cortex will be the main focus of the present review. This part of the prefrontal cortex in rats can be further divided into at least four cytoarchitectonically distinct areas: the medial precentral area (PrCm) or area Fr2, the anterior cingulate area, the prelimbic area, and the infralimbic area [105], [203]. However, on the basis of several anatomical criteria it has been suggested that there exists a main subdivision of the medial prefrontal cortex into a dorsal component, encompassing the FR2, dorsal anterior cingulate areas, and the dorsal part of the prelimbic area, and a ventral component that includes the ventral prelimbic, infralimbic and medial orbital areas (Fig. 1) [11], [74], [191], [220]. Such a distinction between dorsal and ventral subdivisions might be traced back to a phylogenetic origin and, most importantly in the context of the present review, the literature appears to provide ample indications for a concomitant functional–behavioral differentiation of the medial prefrontal cortex into dorsal and ventral parts.
As indicated above, in the context of the present account it is important to realize that the prefrontal cortex evolved from both an archicortical and paleocortical origin [142]. From the archicortical portion arose proisocortical areas 24 (anterior cingulate), 25 (infralimbic), and 32 (prelimbic), which gave rise to both the dorsomedial and dorsolateral prefrontal regions in primates. In fact, the prelimbic cortex of rodents (especially rats) is the equivalent of Brodmann's area 32 in primates (especially macaques) [200]. In the context of the developmental and evolutionary trends recognized by Pandya and colleagues [7], [142], it may be stated that the infralimbic cortex forms the architectonically least developed prefrontal cortical area whereas there is a trend towards further cytoarchitectonic differentiation, as expressed by a clearer and more distinct segregation of cortical layers in the prelimbic and the more dorsally located anterior cingulate and Fr2 areas [105], [106], [203].
In the present review, we will first summarize a series of studies demonstrating that the dorsal and ventral subregions of the medial prefrontal cortex may be involved in different behavioral functions or different aspects of the same function. We will then hypothesize that such a functional distinction is associated with differences not only in cytoarchitectonics, but also in connectivity patterns, neurochemistry and expression of immediate early genes. This review will conclude with the suggestion that because of chemo-anatomical differences in the dorso-ventral axis of the rat medial prefrontal cortex, neurons originating from deep layers of the prelimbic cortex may control a different aspect of subcortical function compared with neurons originating from the superficial layers of the anterior cingulate cortex.
Section snippets
Are there functional grounds for a dissociation between subterritories of the medial prefrontal cortex in the rat?
The medial prefrontal cortex as a whole has been traditionally implicated in attentional processes, working memory and behavioral flexibility. However, a growing body of evidence is currently pointing towards the relevance of conducting a functional analysis of medial prefrontal subregions and supports the contention that the medial frontal cortical wall is characterized by its own functional heterogeneity. In the following paragraphs we will review the recent literature with the intent to
Are there anatomical grounds for a dissociation between subterritories of the medial prefrontal cortex in the rat?
As described in Section 1, the medial prefrontal cortex in rats consists of several cytoarchitectonically distinct subregions that, at least in part, can also be differentiated on the basis of distinct afferent and efferent connectivity patterns with cortical areas as well as with subcortical structures such as the striatum, thalamus, amygdala, hypothalamus and several brain stem nuclei [8], [31], [60], [61], [77], [105], [106], [112], [161], [183], [200], [205]. Although in most of these
Dopamine
As mentioned above (Section 3.4), studies have elegantly demonstrated that the dopamine transporter is densely distributed in the anterior cingulate cortex and only sparsely into the deep layers of the prelimbic cortex [184]. Moreover, these observations are consistent with the lower immunoreactivity and mRNA signal for the dopamine transporter in the ventral tegmental area compared with the substantia nigra [30], [186]. Both anatomical [204] and neurochemical [195] studies indicate that the
Conclusions
The present work reviewed behavioral, neuroanatomical, neurochemical and histochemical evidence to support the existence of a dorso-ventral dissociation within the rat medial prefrontal cortex. The overview of the connectivity of the medial prefrontal cortex leads to the conclusion that this part of the prefrontal cortex can be subdivided not only on the basis of cytoarchitectonics, but also on the basis of differences in connectivity patterns. Borders of cortical areas with similar patterns of
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