Participation of hippocampal metabotropic glutamate receptors, protein kinase A and mitogen-activated protein kinases in memory retrieval

The ability to recall past events is a major determinant of survival strate gies in all species and is of paramount importance in determining our uniqu eness as individuals. In contrast to memory formation, the information abou t the molecular mechanisms of memory retrieval is surprisingly scarce and f ragmentary. Here we show that pretest inhibition of the specific upstream a ctivator of mitogen-activated protein kinase kinase, or of protein kinase A in the hippocampus, blocked retrieval of long-term memory for an inhibitor y avoidance task, a hippocampal-dependent learning task. An activator of pr otein kinase A enhanced retrieval. Mitogen-activated protein kinase activat ion increased in the hippocampus during retrieval, while protein kinase A a ctivity remained unchanged, Pretest intrahippocampal blockade of metabotrop ic glutamate receptors or alpha-amino-3-hydroxy-5-methyl-4-isoxazolone prop ionic acid/kainate receptors, but not N-methyl-D-aspartate receptors or cal cium/calmodulin dependent-protein kinase II, impaired retrieval. Thus, reca ll of inhibitory avoidance activates mitogen-activated protein kinase, whic h is necessary, along with metabotropic glutamate receptors, alpha-amino-3- hydroxy-5-methyl-4-isoxazolone propionic acid/kainate receptors, and protei n kinase A, for long-term memory expression. Our results indicate that memo ry formation and retrieval mag share some molecular mechanisms in the hippo campus. (C) 2000 IBRO, Published by Elsevier Science Ltd, All rights reserv ed.