Involvement of the hippocampal glutamatergic system in shortterm memory

In a previous report we demonstrated that neonatal administration of monosodium glutamate induced specific degeneration of hippocampal pyramidal cells in the CA1 region of Wistar rats during adulthood. Further evidence of hippocampal, especially glutamatergic, involvement in short-term memory will be presented in this article. 1. Trimethyltin (TMT) induced similar degeneration of the hippocampus, which was followed by decreased levels of glutamate in this region at 4 weeks after the TMT administration. With this model the increase in correct response rate for radial maze learning was significantly suppressed in comparison with that of the control animals when TMT was administered at 4 weeks before starting the acquisition trial. Such suppression was followed by a lower response rate in the retention test. On the other hand, the correct response rates in retention tests were not affected when TMT was administered after completion of the acquisition trial. 2. Intrahippocampal administration of D-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) and d-2-amino-5-phosphonopentanoate (AP-5), antagonists of the NMDA subtype of glutamate receptor, impaired the acquisition of discrimination learning, whereas 6,7-dinitroquinoxaline-2,3-dione (DNQX), an antagonist of non-NMDA receptor, did not. 3. Glutamate receptor antisense oligodeoxynucleotide also impaired the acquisition of discrimination learning when infused for 6 days into the hippocampus. These findings suggest that the hippocampus had a significant function in the short-term memory phase and that the glutamatergic system, especially the NMDA subtype of glutamate receptor, was involved in the processes of learning and memory.