Amnesia of reactivation, new learning and second learning

Memory refers to the retention of learned information or experiences in the brain. It is known that interference of certain brain functions immediately after training or memory reactivation can cause memory loss (i.e. amnesia). The post-training process is called consolidation and the post reactivation process is called reconsolidation. However, it remains unclear as to: (1) whether appetitive, goal-directed memories undergo reconsolidation, (2) whether overtrained memories undergo reconsolidation, (3) what the nature of amnesia is (i.e. whether it represents storage or retrieval impairment), (4) how to test the nature of amnesia, and (5) whether the brain uses the same mechanism for a new learning and from a second learning. This thesis, composed of five manuscripts, aims to answer these questions. In the first manuscript, the model of incentive learning of appetitive outcomes in instrumental conditioning was used. Protein synthesis inhibitor (PSI) was infused into lateral and basal amygdala (LBA) after the new incentive learning and after the reactivation of the memory. The results show that appetitive memories in controlling goal-directed behaviors underwent consolidation and reconsolidation in the LBA. In the second manuscript, rats were overtrained with auditory fear conditioning and received intra-LBA PSI infusions after memory reactivation. The results show that only old, but not recent, overtrained auditory fear memories underwent reconsolidation. This suggests overtraining sets a boundary condition on memory reconsolidation. Further results showed dorsal hippocampus and intra-LBA NR2B-subunit containing N-methyl-D-aspartic acid receptors (NMDAr) were involved in this boundary condition. In the third manuscript, the unresolved debate about the nature of amnesia was reviewed from a historical perspective and the suggestions on reconciling this issue are proposed. In the fourth manuscript, a new approach was used to test the nature of amnesia in contextual fear conditioning. Because NMDAr blockade impairs a new learning but not a second learning, it is predicted that if a memory is not stored then the second learning should be impaired by NMDAr blockade. The results suggest amnesia of contextual fear memory caused by intra-dorsal hippocampus (dH) PSI infusion represents a storage impairment which gives a different result from extinction induced irretrievability. In the fifth manuscript , the aim is to identify the brain mechanism for the second learning as the previous manuscript suggests it is different from the first learning mechanism. The results show that the first, but not the second learning required voltage-dependent calcium channels and activation in dH. The second learning was impaired by intra-dH or ventral hippocampus (vH) inactivation only when the protein synthesis in the other portion of hippocampus was blocked after training. This suggests while the first learning by default requires dH, the second learning can be acquired through a functional dH or vH. In summary, this thesis extends memory research from consolidating a new learning to characterizing the reconsolidation of appetitive and overtrained memory to consolidating a second learning which will lead to a more complete description of memory process.

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