Time-dependent reorganization of brain circuitry underlying long-term memory storage

Retrogade amnesia observed following hippocampal lesions in humans and anim als is typically temporally graded(1,2), with recent memory being impaired while remote memories remain intact, indicating that the hippocampal format ion has a time-limited role in memory storage(3,4). However, this claim rem ains controversial because studies involving hippocampal lesions tell us no thing about the contribution of the hippocampus to memory storage if this r egion was present at the time of memory retrieval(5,6). We therefore used n on-invasive functional brain imaging using (C-14)2-deoxyglucose uptake to e xamine how the brain circuitry underlying long-term memory storage is reorg anized over time in an intact brain. Regional metabolic activity in the bra in was mapped in mice tested at different times for retention of a spatial discrimination task. Here we report that increasing the retention interval from 5 days to 25 days resulted in both decreased hippocampal metabolic act ivity during retention testing and a loss of correlation between hippocampa l metabolic activity and memory performance. Concomitantly, a recruitment o f certain cortical areas was observed. These results indicate that there is a time-dependent reorganization of the neuronal circuitry underlying long- term memory storage, in which a transitory interaction between the hippocam pal formation and the neocortex would mediate the establishment of long-liv ed cortical memory representations.