Hippocampal microtubule-associated protein-2 alterations with contextual memory

Using immunohistochemistry and immunoblots, we show that alterations in hip pocampal microtubule-associated protein-2 appear to be highly correlated wi th contextual memory as measured by significantly heightened fear responses . Compared to naive controls, rats trained in a novel context showed signif icantly increased immunostaining for the high molecular weight microtubule- associated protein-2a/b. This increase was observed 2 weeks after training and it was selective for hippocampal CA1 and CA2 pyramidal cells. Pre-expos ure to the training context one month before training altered the hippocamp al microtubule-associated protein-2 response; in these animals only the den tate gyrus showed significantly increased microtubule-associated protein-2a /b. Training-related increases in immunohistochemical staining for microtub ule-associated protein-2 suggested that there was an increase in overall in tact protein, an increase in immunoreactive breakdown products, or changes in protein compartmentalization. Immunoblots of hippocampal homogenates rea cted with monoclonal antibodies to microtubule-associated protein-2a/b show ed an increased presence of breakdown products in trained animals compared to untrained controls. Additional immunoblot studies demonstrated statistic ally significant decreases in the levels and/or phosphorylation state of th e low molecular weight microtubule-associated protein-2c in the hippocampus of trained animals as compared to that of controls. These alterations in m icrotubule-associated protein-2 may reflect dendritic remodeling related to contextual memory storage. (C) 1999 Elsevier Science B.V. All rights reser ved.