Learning and memory impairment in rats with chronic atypical absence seizures.
Atypical absence seizures (AASs) represent a pediatric malignant seizure type that commonly exists as a component of Lennox-Gastaut syndrome. AAS involves both the hippocampal and thalamocortical circuitry in slow spike-and-wave discharges (SSWD) and is associated with cognitive dysfunction. The electrographic, behavioral, and pharmacological features of clinical AAS have been reproduced in rats chronically in the AY-9944 (AY) model. AY rats show spontaneous SSWD involving the hippocampus, a structure that is highly implicated in learning and memory. The purpose of the present study was to determine whether AY rats exhibit cognitive deficits that mirror those observed in AAS clinically. Hippocampal function was examined in AY animals both in vitro with electrophysiology (i.e., synaptic plasticity) and in vivo with a hippocampus-dependent radial arm maze (RAM) task that is designed to assess spatial cognition. In vitro tests of synaptic plasticity revealed impairments in long-term potentiation (LTP), paired-pulse facilitation (PPF), and presynaptic depression (PD). Consistently, performance of AY animals in RAM revealed fewer perfect entries, a greater number of errors, and required more training days to learn the task than saline-treated controls. The abolishment of spontaneous seizures by ethosuximide failed to recover the perturbed spatial learning and working memory in AY animals. AY rats demonstrate altered hippocampal functioning as manifested by altered synaptic plasticity and cognition. The relationship between AAS and cognitive deficit remains uncertain and the pathophysiology of both in AY treated requires further investigation.
Chan
Katherine F Y
KF
Division of Neurology, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.
Jia
Zhengping
Z
Murphy
Patricia A
PA
Burnham
W McIntyre
WM
Cortez
Miguel A
MA
Snead
O Carter
OC
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009924:Organ Culture Techniques; D051381:Rats; D020318:Rats, Long-Evans