Time-dependent reorganization of the brain components underlying memory retention in trace eyeblink conditioning

Many studies have confirmed the time-limited involvement of the hippocampus in mnemonic processes and suggested that there is reorganization of the responsible brain circuitry during memory consolidation. To clarify such reorganization, we chose trace classical eyeblink conditioning, in which hippocampal ablation produces temporally graded retrograde amnesia. Here, we extended the temporal characterization of retrograde amnesia to other regions that are involved in acquisition during this task: the medial prefrontal cortex (mPFC) and the cerebellum. At a various time interval after establishing the trace conditioned response (CR), rats received an aspiration of one of the three regions. After recovery, the animals were tested for their CR retention. When ablated 1 d after the learning, both the hippocampal lesion and the cerebellar lesion group of rats exhibited a severe impairment in retention of the CR, whereas the mPFC lesion group showed only a slight decline. With an increase in interval between the lesion and the learning, the effect of the hippocampal lesion diminished and that of the mPFC lesion increased. When ablated 4 weeks after the learning, the hippocampal lesion group exhibited as robust CRs as its corresponding control group. In contrast, the mPFC lesion and the cerebellar lesion groups failed to retain the CRs. These results indicate that the hippocampus and the cerebellum, but only marginally the mPFC, constitute a brain circuitry that mediates recently acquired memory. As time elapses, the circuitry is reorganized to use mainly the mPFC and the cerebellum, but not the hippocampus, for remotely acquired memory.