Involvement of the rat prefrontal cortex in cognitive functions: A central role for the prelimbic area

Psychobiology 2000, 28 (2), 229-237 Involvement of the rat prefrontal cortex in cognitive functions: A central role for the prelimbic area SYLVIE GRANON Institut Pasteur, Paris, France and BRUNO POUCET CRNC, CNRS, MarseiUe, France In this brief review, we address the cognitive functions of a subregion of the rat frontal cortex, the prelimbic cortex. Growing evidence suggests that the prelimbic cortex is involved in working memory, defined as the temporary storage of information required for its internal manipulation. However, several factors appear to modulate the extent to which prelimbic damage impairs performance in delayed tasks. These factors, which contribute to the overall difficulty of the task, are related to the attentional requirement of the task and to the response selection mechanisms that underlie correct performance. Impairments induced by prelimbic cortical damage are increased when the task requires the rat to consistently focus its attention on the detection of external events and when the learning rule countradicts either spontaneously used or previously learned strategies. This overall pattern of deficit suggests that the prelimbic cortex is not a pure working memory system. Rather, it subtends a wide range of processes that are required for solving difficult problems. Together with anatomical evidence, the existence of functional similarities between the prelimbic cortex of the rat and the dorsolateral prefrontal cortex of primates suggests some homology between these regions across species. Therefore, the rat prelimbic cortex appears to provide a valuable model system for studying the precursors of higher level cognitive processes in nonhuman and human primates. While the role of the cortex in learning and memory has long been acknowledged in the rat (Lashley, 1929), it is only relatively recently that a regional analysis of its functions has been undertaken. This is especially true for the prefrontal cortex probably because its involvement in a specific learning process is hard to determine. One reason for this difficulty is that the frontal cortex is not a homogeneous area. Therefore, its damage induces mixed patterns of impaired and spared abilities depending on the exact locus of the lesion, often making difficult the interpretation of results drawn from different studies. I In the present review, we focus on a subregion of the rat medial prefrontal cortex, the pre limbic cortex (PL), an area currently thought to be homologous to the dorsolateral prefrontal cortex of human and nonhuman primates. In the primate literature, the dorsolateral prefrontal cortex has recently received much attention with regard to its possible role in a category of high-level cognitive processes, usually referred to as executive functions. Such functions Support for this work was provided by the Pasteur Institute and the French National Center for Scientific Research. We thank two anonymous referees for their helpful comments on an earlier version of this paper. Correspondence should be addressed to S. Granon, Departement de Virologie Moleculaire, Institut Pasteur, 25 rue du Dr. Roux, 75075 Paris, France (e-mail: ). are hypothesized to underlie human problem solving and refer to complex cognitive processes required to perform flexible and voluntary goal-directed behaviors based on stored information in accordance with the context (Stuss & Benson, 1983). Executive functions rely on a set of distinctive processes, such as working memory, attentional capacities, and response-selection mechanisms, all of which are necessary for successful problem solving. Early research of the medial prefrontal cortex in rodents, which includes the prelimbic area, is consistent with at least some function in working memory (see Kolb, 1990, for review). It is not clear, however, whether its other functional properties can be described along the lines suggested by the theory of executive functions developed in the primate literature. Our purpose in this article is to attempt to bridge the rat and primate literature with regard to the putative cognitive functions of the PL. To do so, we briefly discuss evidence that human executive functions involve the dorsolateral prefrontal cortex (DLPFC). We then describe recent experimental data obtained in the rat so as to examine whether the rat PL is involved in working memory. We further ask whether, within working memory, the prelimbic function is best characterized by its involvement in a certain type of processing (e.g., maintaining information across a delay or manipulating such information to select a response) or by its involvement in 229 Copyright 2000 Psychonomic Society, Inc. 230 GRANON AND POUCET processing certain types of information (e.g., spatial vs. nonspatial information). Lastly, we will briefly describe the results of a few experiments that have addressed the involvement of the pre limbic cortex in attentional functions. PREFRONTAL CORTEX AND EXECUTIVE FUNCTIONS IN HUMANS AND NONHUMAN PRIMATES As stated above, executive functions support flexible goal-directed behaviors based on stored information. Initially, relevant information must be selected from the environment through some multimodal sensorial filter (i.e., attentional mechanisms). To be internally manipulated, information then needs to be temporally organized and stored in a temporary memory buffer (i.e., working memory). Finally, appropriate decisions regarding the use of this information in this particular context must be made (i.e., response-selection function). Each of these processes seems to depend on the DLPFC, as shown by studies of patients with prefrontal lesions and by recent imaging studies as well as by behavioral and electrophysiological data from primates (Fuster, 1997; GoldmanRakic, 1990; Grafman, 1994; Miller, 1999). Although it has long been thought that working memory processes within the frontal cortex are organized according to the nature of information being processed (e.g., with spatial information processed within the DLPFC; Goldman-Rakic, 1987), this view has recently been challenged. Specifically, recent functional brain imaging studies have suggested that the subdivision ofthe human prefrontal cortex in dorsal and ventral regions may be reconsidered according to the type of processing achieved in each region (D'Esposito, Aguirre, Zarahn, Ballard, Shin, & Lease, 1998; Owen et aI., 1999). In other words, the function of the different prefrontal areas may depend on the type of processing performed on the information more than on the type of information (spatial vs. nonspatial information). For example, D'Esposito and collaborators (1998) showed that both spatial and nonspatial working memory tasks may result in prefrontal activation of the same regional area when tested in tasks that tap the same type of processing. In contrast, they reported that the ventral areas of the human prefrontal cortex are selectively activated when the subjec (...truncated)