Pretraining and the function of hippocampal long-term potentiation.

Abstract

The pretraining studies show that rats can encode new spatial memory without NMDA receptor–mediated LTP. This suggested to many that LTP and memory were not related and that behavioral impairments in the naive condition reflected the disruptive sensorimotor effects of the drugs. New data suggest that (1) sensorimotor dysfunction does not explain the impaired performance after NMDA receptor blockade in naive rats, (2) the effectiveness of pretraining depends on the subsequent training protocol in the water maze, and (3) spatial representations in the hippocampus are normally maintained by NMDA receptor–mediated LTP. This does not preclude that there are additional NMDA receptor–independent memory mechanisms whose function may be sufficient to encode pure spatial relations under simplified conditions, such as after pretraining. When the complexity of the spatial memory task is increased, e.g., by requiring retention of temporal order, these back-up mechanisms may no longer help.*To whom correspondence should be addressed (e-mail: edvard.moser@svt.ntnu.no).