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Learning initiates a series of plastic events the occurrence of which are required for the storage of information related to the training experience. Several lines of evidence indicate that, in the rat hippocampus, different members of the family of mitogen-activated protein kinases (MAPK) play a key role in the onset of such plastic events. Using SP600125, the newly developed inhibitor of the MAPK c-Jun amino-terminal kinase (JNK), we show a direct involvement of this protein kinase in mnemonic processes. The intra-CA1 infusion of SP600125, at a dose that in naïve animals significantly reduced the phosphorylation levels of c-Jun without affecting the activity of ERK1/2 or p38 MAPK, enhanced short-term memory (STM) but blocked long-term memory (LTM) formation and retrieval of an inhibitory avoidance learning task. No action of this drug on locomotor/exploratory activity or general anxiety state could be detected. The significance of these results is discussed in the context of others describing the independence of LTM from STM.

Memories are extinguished by the repeated presentation of a conditioned stimulus in the absence of an unconditioned stimulus to which it has been associated. It is believed that extinction establishes a new hierarchy of responses rather than an actual forgetting of the original response, which can usually reappear spontaneously after interruption of the extinction process. In this study, our aim was to analyze how profound extinction can be. Rats were trained in a one-trial, step-down inhibitory avoidance paradigm and then were exposed to several extinction sessions in which they were allowed to freely explore the apparatus for 30 sec after having stepped down. Extinction was complete enough so that there was no spontaneous recovery, and test session performance could not be enhanced by pharmacological agents with well known facilitative actions on retrieval. After being submitted to a new training session, control animals reacquired the avoidance response; however, animals failed to do so after receiving bilateral intra-CA1 infusions of either the protein synthesis inhibitor anisomycin or the mRNA synthesis blocker 5,6-dichloro-1-␤-d-ribofuranosyl benzimidazole 15 min before the retraining session. Our results indicate that extinction can be carried to a point at which reinstallment of the conditioned response requires, like the original learning, de novo gene expression and protein synthesis in the CA1 region of the dorsal hippocampus.

Several lines of evidence suggest that glutamate receptors are involved in memory processing. To examine the role of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors on memory consolidation, rats were bilaterally implanted with cannulae aimed at the CA1 region of the dorsal hippocampus (CA1), entorhinal cortex (ENTO), posterior parietal cortex (PPC) or the basolateral nucleus of the amygdala (BLA), and trained in a one-trial step-down inhibitory avoidance task. At different times after training, the alpha-amino 3-hydroxy-5 methyl 4-isoxazole propionate (AMPA) receptor blocker, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (1.0 microg/side), or the metabotropic type-I receptor antagonist, 2-amino-3-phosphonopropionic acid (AP3) (1.0 microg/side), were infused into the above-mentioned structures. CNQX produced retrograde amnesia when infused into BLA or CA1 0, 30, 90 or 180 min post-training but not at later times. AP3 blocked memory consolidation when administered into CA1 0, 30 or 180 min post-training, while in BLA, it was amnestic only when given 0 or 30 min after the training session. CNQX and AP3 had no effect on memory when administered into ENTO or PPC at any time. Our data suggest that the consolidation of the avoidance memory requires intact non-NMDA receptor function in the hippocampus and the basolateral nucleus of the amygdala, but not necessarily in the entorhinal and parietal cortex, for long periods after training.

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