Do rats have prefrontal cortex? The rose-woolsey-akert program reconsidered.

Abstract Primates are unique among mammals in possessing a region of dorsolateral prefrontal cortex with a well-developed internal granular layer. This region is commonly implicated in higher cognitive functions. Despite the histological distinctiveness of primate dorsolateral prefrontal cortex, the work of Rose, Woolsey, and Akert produced a broad consensus among neuroscientists that homologues of primate granular frontal cortex exist in nonprimates and can be recognized by their dense innervation from the mediodorsal thalamic nucleus (MD). Additional characteristics have come to be identified with dorsolateral prefrontal cortex, including rich dopaminergic innervation and involvement in spatial delayed-reaction tasks. However, recent studies reveal that these characteristics are not distinctive of the dorsolateral prefrontal region in primates: MD and dopaminergic projections are widespread in the frontal lobe, and medial and orbital frontal areas may play a role in delay tasks. A reevaluation of rat frontal cortex suggests that the medial frontal cortex, usually considered to be homologous to the dorsolateral prefrontal cortex of primates, actually consists of cortex homologous to primate premotor and anterior cin-date cortex. The lateral MD-projection cortex of rats resembles portions of primate orbital cortex. If prefrontal cortex is construed broadly enough to include orbital and cingulate cortex, rats can be said to have prefrontal cortex. However, they evidently lack homologues of the dorsolateral prefrontal areas of primates. This assessment suggests that rats probably do not provide useful models of human dorsolateral frontal lobe function and dysfunction, although they might prove valuable for understanding other regions of frontal cortex.