Impaired hippocampal memory function and synaptic plasticity in experimental cortical dysplasia

Abstract

Memory impairment is a common comorbidity in people with epilepsy-associated malformations of cortical development. We studied spatial memory performance and hippocampal synaptic plasticity in an animal model of cortical dysplasia. Embryonic day 17 rats were exposed to 2.25 Gy external radiation. One-month-old rats were tested for spatial recognition memory. After behavioral testing, short-term and long-term synaptic plasticity in the hippocampal CA1 region was studied in an in vitro slice preparation. Behavioral assessments showed impaired hippocampal CA1-dependent spatial recognition memory in irradiated rats. Neurophysiologic assessments showed that baseline synaptic transmission was significantly enhanced, whereas paired-pulse facilitation, long-term potentiation, and long-term depression of the field excitatory postsynaptic potential (fEPSP) slope at Schaffer collateral/commissural fiber-CA1 synapses were significantly reduced in the irradiated rats. Histologic observations showed dysplastic cortex and dispersed hippocampal pyramidal neurons. This study has shown that prenatally irradiated rats with cortical dysplasia exhibit a severe impairment of spatial recognition memory accompanied by disrupted short-term and long-term synaptic plasticity and may help to guide development of potential therapeutic interventions for this important problem.