NMDA receptor activity in learning spatial procedural strategies: I. The influence of hippocampal lesions

To acquire knowledge about the environment two types of learning are necessary: declarative localizatory learning about where environmental cues and the subject are, and procedural learning about how to explore and move around the environment. Experimental data indicate that hippocampal regions are involved in spatial learning, playing a key role in building spatial cognitive maps. The contribution of hippocampal NMDA receptors to spatial functions is indicated by the disruption of place learning when NMDA long-term potentiation is blocked. Conversely, the hippocampal contribution to the acquisition of procedural strategies is still controversial. Inactivation of the hippocampus by antagonizing the activity of AMPA/kainate receptors results in impaired spatial procedural learning. However, in the presence of a blockade of NMDA long-term potentiation in hippocampal areas it is still possible to learn explorative strategies. To investigate the involvement of the hippocampal NMDA receptors in spatial procedural learning, an NMDA receptor antagonist (CGS 19755) was administered i.p. to unlesioned animals or to animals with total ablation of hippocampal structures that had been tested in the Morris water maze. The CGS administration induced peripheral circling in both unlesioned control animals and in rats with bilateral hippocampal ablation. Conversely, circling was not observed if the drug-treated animals (either unlesioned or lesioned) had been spatially trained before drug administration. These findings indicate that even in the absence of the hippocampal formation the NMDA receptor antagonist found a site of action to influence the acquisition of spatial procedures to search for the platform.