Cellular Mechanisms of Working Memory and its Modulation by Dopamine in the Prefrontal Cortex of Primates and Rats

Abstract

It is often assumed that the massive expansion of the prefrontal cortex (PFC) in humans and nonhuman primates was a pivotal determinant of evolutionary success. Whereas dorsolateral prefrontal cortical areas in macaque monkeys and humans share multiple characteristics with regard to cytoarchitecture, hodology (Petrides and Pandya, 1999), and DA innervation (Lewis and Sesack, 1997), the organization of the frontal cortex and its dopaminergic innervation are vastly different in rats and primates (Berger et al., 1991; Preuss, 1995; Williams and Goldman-Rakic, 1998; Uylings et al., 2003). This raises the question of whether certain properties of the primate PFC are not present, or only represented in a rudimentary fashion in other species. Seminal findings from brain lesion and behavioral electrophysiology studies determined that different subregions of the PFC engage in distinct cognitive functions. Among these findings is the observation that cells in the dorsolateral PFC regions exhibit persistent activity in response to external stimuli, after the stimuli have ceased. This activity may reflect the ability to temporarily hold items in working memory (WM), a cognitive function required for the temporal organization of behavior (Fuster, 1997). Persistent activity is believed to be maintained through recurrent excitation in assemblies of PFC neurons. In the primate PFC, such cell assemblies may be organized into interconnected stripe-like clusters, similar to the columns in primary sensory cortex. By means of persistent firing, the PFC is thought to transiently store stimulus-related information that is task-relevant, for example, “what” an object is, or “where” it is located. Thus, primate PFC neurons are said to