Differential involvement of hippocampal G-protein subtypes in the memory process of rats

Inactivation of G i and G o proteins in the dentate gyrus of the hippocampus by pertussis toxin did not affect memory retention of a one-way passive avoidance learning task in rats. Interference of normal G s activity in the dentate gyrus by cholera toxin impaired retention performance dose-dependently. Cholera toxin also antagonized the memory-enhancing effect of corticotropin-releasing factor in the hippocampus. However, although G i and G o proteins are probably not involved in the memory consolidation process per se, in animals showing a full retention score there was a significant and long-lasting increase of G o concentration in the dentate gyrus. Results of ADP-ribosylation experiments have shown that there was a dose-dependent decrease of ADP-ribosylation in vitro as the concentration of in vivo pertussis toxin and cholera toxin increased. These results together suggest that G s protein is probably involved in the initiation of the memory consolidation process, while enhanced G o expression is the ultimate result upon memory formation. These results provide the first in vivo evidence relating the functions of hippocampal G proteins to the memory process of mammals.