Spatial learning deficits without hippocampal neuronal loss in a model of early-onset epilepsy

C. L. Lee, J. Hannay, R. Hrachovy, S. Rashid, B. Antalffy, J. W. Swann

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Studies were undertaken to examine the effects recurrent early-life seizures have on the ability of rats to acquire spatial memories in adulthood. A minute quantity of tetanus toxin was injected unilaterally into the hippocampus on postnatal day 10. Within 48 h, rats developed recurrent seizures that persisted for 1 week. Between postnatal days 57 and 61, rats were trained in a Morris water maze. Toxin-injected rats were markedly deficient in learning this task. While these rats showed gradual improvement in escape latencies over 20 trials, their performance always lagged behind that of controls. Poor performance could not be explained by motor impairments or motivational difficulties since swimming speed was similar for the groups. Only eight of 16 toxin-injected animals showed focal interictal spikes in the hippocampus during electroencephalographic recordings. This suggests that learning deficiencies and chronic epilepsy may be independent products of recurrent early-life seizures. A quantitative analysis of hippocampus revealed a significant decrease in neuronal density in stratum pyramidale of experimental rats. However, the differences were largely explained by a concomitant increase in the area of stratum pyramidale. Studies of glial fibrillary acidic protein expression and spread of horseradish peroxidase-conjugated tetanus toxin in the hippocampus suggest that the dispersion of cell bodies in stratum pyramidale can neither be explained by a reactive gliosis nor the direct action of the toxin itself. Taken together, we suggest that recurrent seizures beginning in early life can lead to a significant deficiency in spatial learning without ongoing hippocampal synchronized network discharging or a substantial loss of hippocampal pyramidal cells.

Original languageEnglish (US)
Pages (from-to)71-84
Number of pages14
JournalNeuroscience
Volume107
Issue number1
DOIs
StatePublished - Nov 9 2001
Externally publishedYes

Keywords

  • Learning and memory
  • Morris water maze
  • Neonates
  • Pyramidal neurons
  • Tetanus toxin

ASJC Scopus subject areas

  • Neuroscience(all)

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