RETRIEVAL ASSOCIATED CHOLINERGIC ACTIVITY AND ITS INHIBITION BY MEMORY UPDATING

Both hippocampal cholinergic and glutamatergic systems are believed to be engaged in learning and memory. By measuring behavior and ex vivo second messenger inositol phosphate (IP) accumulation, we investigated biochemical responses of cholinergic receptors to retrieval and acqui sition processes in rats trained in a spatial task. We report that in rats retrieving spatial information, carbachol-induced IP accumulation strongly and transiently increased above values observed in handled c ontrols and rats acquiring new information, and that this increase was profoundly inhibited by N-methyl-D-aspartate (NMDA). These results su ggest that memory retrieval, rather than formation of a memory trace, is related to increased responsiveness of the hippocampal cholinergic system, and that formation of a new memory trace, which updates long-t erm memory, inhibits this cholinergic activation, possibly by a learni ng-associated increase in NMDA receptor activation. Moreover, the pres ent study shows that the distinction between acquisition and retrieval processes can be demonstrated on both a behavioral and biochemical le vel.