Organization of retrosplenial cortical projections to the anterior cingulate, motor, and prefrontal cortices in the rat
Introduction
The retrosplenial cortex, which occupies the caudal half of the cingulate cortex in the rat, consists of four cytoarchitectonically distinct areas: 29a, 29b, 29c and 29d (Vogt and Peters, 1981, Vogt, 1993). The relatively small areas 29a and 29b are located at levels caudal to the splenium of the corpus callosum, whereas the relatively larger areas 29c and 29d extend almost throughout the rostrocaudal axis of the retrosplenial cortex (see Fig. 1 for reference).
Recent studies show that either cytotoxic lesions involving the entire retrosplenial cortex, or even those restricted to its caudal parts, cause spatial memory impairment (Vann and Aggleton, 2002, Vann et al., 2003). Electrophysiological evidence also supports the idea that this region is involved some way in spatial memory or associated functions. Cells in the retrosplenial cortex have been implicated in encoding the head direction (Chen et al., 1994a, Chen et al., 1994b) or the combinations of direction, location, and movement of an animal (Cho and Sharp, 2001); retrosplenial cells have also been implicated in path integration associated with spatial navigation (Cooper and Mizumori, 1999, Cooper et al., 2001). Thus, the retrosplenial cortex may play critical roles in spatial memory and navigation. It is assumed that the retrosplenial cortex transmits such spatial information via corticocortical pathways to the frontal association and/or motor cortical regions, which are intimately involved in spatial and motor behaviors (e.g. Hall and Lindholm, 1974, Becker et al., 1980).
The corticocortical projections from the retrosplenial cortex to the frontal cortical regions thus far reported in the literature indicate that the region including areas 29a and 29b projects to areas 24a and 32 (Van Groen and Wyss, 1990), that area 29c projects to areas 24a and 24b (Vogt and Miller, 1983, Van Groen and Wyss, 2003), and that area 29d projects to areas 24a and 24b, the orbital cortex, and the medial part of the secondary motor area (Vogt and Miller, 1983, Van Groen and Wyss, 1992). However, the projections from the caudal part of the retrosplenial cortex, a region that is particularly important for spatial memory, are still unclear. For example, it is as yet undetermined whether projections from area 29a differ from those originating from area 29b. Furthermore, to date, projections to motor areas have not been studied in detail (Vogt and Miller, 1983, Van Groen and Wyss, 1992).
Thus, the present study was carried out to clarify in more detail the organization of projections from each area of the retrosplenial cortex to the anterior cingulate, motor, and prefrontal cortices in the rat. First, using the anterograde neuronal tracer biotinylated dextran amine (BDA), we determined the terminal distribution of projections originating from each area of the retrosplenial cortex. Second, using the retrograde neuronal tracer cholera toxin B subunit (CTb), we determined the distribution of cells of origin of these projections. The results show that each area of the retrosplenial cortex projects to distinct parts of the anterior cingulate, motor, and prefrontal cortices.
Section snippets
Materials and methods
A total of 45 Wistar rats of both sexes, weighing 210–460 g, were used in the present study. All surgical procedures were done under deep anesthesia consisting of intraperitoneal injections of sodium pentobarbital (60 mg/kg body weight) or a combination of xylazine (10 mg/kg body weight) and ketamine (50 mg/kg body weight). Before and after surgery, the rats were allowed free access to food and water. All the experimental procedures complied with the guidelines of the National Institute of Health
Results
In the anterograde tracing experiments, BDA was injected into each area of the retrosplenial cortex at various rostrocaudal levels in order to delineate terminal fields of retrosplenial cortical projection fibers to frontal cortical regions, such as the anterior cingulate, motor, and prefrontal cortices. The injections involved all cortical layers and were successfully made into area 29a (2 cases), area 29b (1 case), areas 29b and 29c (2 cases), area 29c (11 cases), and area 29d (7 cases). The
Discussion
The present study demonstrated the anatomical organization of projections originating from different cytoarchitectonic areas of the retrosplenial cortex and terminating in frontal cortical regions, specifically the anterior cingulate, motor, and prefrontal cortices. Using sensitive anterograde and retrograde neuronal tracers, we showed that distinct areas of the retrosplenial cortex provide predominantly ipsilateral projections to distinct parts of these frontal cortical regions (Fig. 6).
Acknowledgements
The present study was, in part, supported by a grant (No. 07660400) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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