UC San Diego

The hippocampus plays an important role in memory. Hippocampal subfield CA1 serves as the primary output of the hippocampus to neocortex and thus is important for supporting hippocampal function. Based on this role, a lesion targeting the entire CA1 region should block hippocampal output to neocortex and disrupt hippocampus-dependent memory as severely as a large hippocampal lesion. However, some findings contradict this idea, demonstrating more severe impairments following DG or CA3 lesions than after CA1 lesions. This could be explained by (i) information leaving the hippocampus through descending CA3 projections, or (ii) the incompleteness of existing CA1 lesions, which separately target only dorsal or ventral CA1. Overall, it remains unclear if CA1 output to neocortex is required to support memory.

We resolve this issue with a novel lesion that targets the entire dorsoventral CA1 axis. First, we tested the effect of the lesion on retrograde memory and found that complete CA1 lesions caused severe impairments in the watermaze, context fear conditioning, and trace fear conditioning tasks (similar to previous findings with large hippocampal lesions). We next tested the effect of the CA1 lesion and large hippocampal lesions on anterograde memory. Both lesions impaired performance in the watermaze task and delayed match-to-position (DMP). However, when rats were given prior DMP training, CA1 lesions no longer impaired watermaze performance, and when rats were given prior watermaze training, CA1 lesions no longer impaired DMP performance. In contrast, rats with hippocampal lesions were impaired in both tasks regardless of prior training.

These studies demonstrate that CA1 output to neocortex is normally needed to support memory, but prior experience can ameliorate anterograde memory impairments caused by the loss of CA1 output. Because prior experience only benefited rats with CA1 lesions, we suggest that descending CA3 efferents may be able to support some forms of memory. However, we also consider that CA1 sparing or a reduction in remote lesion effects might also account for the superior CA1 performance. Additionally, we suggest that the concept of the schema may be particularly important for understanding the beneficial effect of prior experience.