Neither time nor number of context-shock pairings affect long-term dependence of memory on hippocampus.

There are still basic uncertainties concerning the role of the hippocampus (HPC) in maintaining long-term context memories. All experiments examining the effects of extensive HPC damage on context memory for a single learning episode find that damage soon after learning results in robust retrograde amnesia. Some experiments find that if the learning-to-damage interval is extended, remote context memories are spared. In contrast, other experiments fail to find spared remote context memory. One possible explanation for inconsistency might be the potency of the context memory conditioning procedure, as the experiments showing spared remote memory used a greater number of context-shock pairings, likely creating a stronger context fear memory. We designed an experiment to directly test the question: does increasing the number of context-shock pairings result in sparing of remote context memory after HPC damage? Six independent groups of rats received either 3 or 12 context-shock pairings during a single conditioning session and then either received extensive HPC damage or Control surgery at 1-week, 2-months, or 4-months after conditioning. 10 days after surgery rats were tested for memory of the shock context. Consistent with all relevant studies, HPC damage at the shortest training-surgery interval produced robust retrograde amnesia for both 3- and 12-shock groups whereas the Control rats expressed significantly high levels of memory. At the longer training-surgery interval, HPC damage produced similarly robust retrograde amnesia in the rats in both the 3- and 12-shock groups. These results clearly demonstrate that increasing the number of context-shock pairings within a single learning session does not change the dependence of the memory on the HPC. Current evidence from our group on retrograde amnesia has now shown that partial damage, dorsal vs. ventral damage, discrete cue+context conditioning, time after training, and number of context-shock pairings do not affect HPC dependence of context fear memories. When taken together, the evidence strongly supports a permanent role of the HPC in context memory.