Hippocampal Lesions in Male Rats Produce Retrograde Memory Loss for Over-Trained Spatial Memory but Do Not Impact Appetitive-Contextual Memory: Implications for Theories of Memory Organization in the Mammalian Brain

J Neurosci Res. 2025 Jan;103(1):e70013. doi: 10.1002/jnr.70013.

Abstract

Evidence suggests that hippocampal (HPC) disruption following learning produces retrograde amnesia on a range of tasks. Many of these tasks do not require HPC function in the anterograde direction suggesting that, in the intact brain, the HPC is actively involved during all forms of learning. However, prior work has also demonstrated double dissociations of HPC and amygdala function, which is inconsistent with this view. Here, we aim to understand this discrepancy by assessing the effects of neurotoxic lesions of the HPC on anterograde and retrograde amnesia for conditioned place preference (CPP). This task is dependent on a network centered on the basolateral amygdala and not the HPC. The results show that extensive HPC damage had no impact on the acquisition or expression of CPP. One explanation for this result is that the task requires multiple, distributed training sessions for conditioning to emerge, and it has been proposed that this parameter may eliminate the need for HPC to support memory. To test this, we completed experiments to probe place learning in the Morris water task, which is thought to always require HPC function, but implemented an over-training procedure before HPC damage. We found that rats were severely impaired suggesting that this task parameter does not always allow non-HPC networks to support learning. Finally, an experiment was designed to test whether memories acquired by distinct memory networks on the same days, within hours of one another, would be linked in HPC. The results showed that they remained independent of one another.

Keywords: conditioned place preference; hippocampus; memory retrieval; retrograde memory; spatial learning.

MeSH terms

  • Amnesia, Retrograde / physiopathology
  • Animals
  • Appetitive Behavior / physiology
  • Basolateral Nuclear Complex / physiology
  • Hippocampus* / physiology
  • Male
  • Rats
  • Rats, Long-Evans*
  • Spatial Memory* / physiology