Retrograde and anterograde amnesic effects of excitotoxic lesions of the rat retrosplenial cortex (RS) and hippocampus (HPC) were investigated. To test retrograde amnesia, rats were trained with two-arm place discrimination in a radial maze 4 wk and 1 d before surgery with a different arm pair, respectively. In the retention test 1 wk after surgery, both lesion groups showed temporally ungraded retrograde amnesia. To test anterograde amnesia, animals were trained after surgery to discriminate three arm pairs successively within a day, and then after interposition of 1-to 4-wk intervals, one of these pairs, respectively, was tested for retention. RS-lesioned rats could acquire these pairs of place discriminations rapidly but showed a retention interval-dependent impairment in the retention test. Conversely, HPC-lesioned rats took more sessions to acquire these pairs than did the control group, and their retention was ∼70% of correct performance regardless of retention interval. Results suggest that RS and HPC have different roles in spatial memory and that RS is important for remote memory process.Recent studies indicate that the retrosplenial cortex (RS) may contribute to spatial learning and memory in humans (Valenstein et al. 1987;Maguire 2001) and rodents (Sutherland et al. 1988; Aggleton 2002, 2004). In addition, the RS might cooperate with the hippocampus (HPC) to engage in spatial learning and memory, since the RS has dense reciprocal neural connections with the hippocampal formation (Vogt 1986;Wyss and van Goren 1992;Burwell and Amaral 1998), which is important for learning and memory, and both RS and HPC contain neurons with spatial firing properties such as "head direction cells" (Chen et al. 1994;Cho and Sharp 2001) and "place cells" (O'Keefe and Nadel 1978). Furthermore, the neural activity of RS affects the hippocampal spatial coding (Cooper and Mizumori 2001) and the hippocampal theta wave activity (Destrade and Ott 1982;Vanderwolf et al. 1985), which is related to learning and memory (Pan and McNaughton 1997). Moreover, fornix transection or HPC lesions caused a reduction of c-Fos expression in RS during radial maze performance (Vann et al. 2000;Albasser et al. 2007).It has been considered that memory function depends on an interaction between HPC and the neocortical areas (e.g., Squire 1992; Eichenbaum et al. 1994;Nadel and Moscovitch 1997). Most of these perspectives assumed that long-term memory is stored in the neocortex. Thus, the RS might be one of the candidate brain regions that form a network with hippocampal formation in memory function, especially in long-term memory processing. However, there were few lesion studies that demonstrated the role of the RS in spatial memory processes and that directly compared the effects of lesions of the RS and HPC. Thus, it remains unclear whether the RS is important for spatial longterm memory and whether the roles of the RS and HPC in spatial memory could be clearly differentiated.Here we compared retrograde and anterograde amnesic effects of RS and HP...