Suppression of neurotoxic lesion-induced seizure activity: evidence for a permanent role for the hippocampus in contextual memory
Loading...
Date
2011
Authors
Sparks, Fraser T.
Lehmann, Hugo
Hernandez, Khadaryna
Sutherland, Robert J.
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Abstract
Damage to the hippocampus (HPC) using the excitotoxin N-methyl-D-aspartate (NMDA) can cause retrograde amnesia for
contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to
cause intense neuronal discharge (seizure activity) during the hours that follow its injection. These seizures may have
detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDAinduced
seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we
developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible
associated seizure activity. NMDA and tetrodotoxin (TTX), a sodium channel blocker, are simultaneously infused into the rat
HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure
activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDAinduced,
or no damage to the HPC at a recent (24 hours) or remote (5 weeks) time point. After recovery, the rats were
placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust
memory for the aversive context at both time points, whereas rats that received NMDA or NMDA+TTX lesions showed a
significant reduction in learned fear of equal magnitude at both the recent and remote time points. Therefore, it is unlikely
that observed retrograde amnesia in contextual fear conditioning are due to disruption of non-HPC networks by
propagated seizure activity. Moreover, the memory deficit observed at both time points offers additional evidence
supporting the proposition that the HPC has a continuing role in maintaining contextual memories.
Description
Sherpa Romeo green journal; open access
Keywords
Contextual memory , Retrograde amnesia , Memory impairments , Seizure activity , Excitotoxin N-methyl-D-aspartate , NMDA , Neurotoxic , Lesion
Citation
Sparks, F. T., Lehmann, H., Hernandez, K., & Sutherland, R. J. (2011). Suppression of neurotoxic lesion-induced seizure activity: Evidence for a permanent role for the hippocampus in contextual memory. PLoS ONE, 6(11), e27426. doi:10.1371/journal.pone.0027426